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Home , Bacampicillin, Balofloxacin, Bekanamycin, Cefacetrile, Cefalexin, Cefaloglycin

Andrew V DeLong, Jared C Harris, Brittany S Larcart, Chandler B Massey, Chelsie D Northcutt, Somuayiro N Nwokike, Oscar A Otieno, Harsh M Patel, Mehulkumar P Patel, Pratik Pravin Patel, Eugene I Rowell, Brandon M Rush, Marc-Edwin G Saint-Louis, Amy M Vardeman, Felicia N Woods, Giso Abadi, Thomas J. Manning

Computational

Valdosta State University is located in South Georgia.

Computational Antibiotics

Index

• Computational Details and Website Access (p. 8)

• Acknowledgements (p. 9)

• Dedications (p. 11)

• Historical Introduction (p. 13)

Introduction to Antibiotic groups • ’s (p. 21)

• (p. 22)

• Oxazolidines (p. 23)

• (p. 24)

• (p. 25)

• Quinolones (p. 26)

• Polypeptides antibiotics (p. 27)

• Glycopeptide Antibiotics (p. 28)

• Sulfonamides (p. 29)

• (p. 30)

• First Generation (p. 31)

• Third Generation (p. 32)

• Fourth-Generation Cephalosporins (p. 33)

• Fifth Generation Cephalosporin’s (p. 34)

• antibiotics (p. 35)

Computational Antibiotics

Antibiotics Covered (in alphabetical order) (p. 36) Cefempidone (p. 98) (p. 159) (p. 38) (p. 100) (p. 161) (p. 40) (p. 102) Ceftoxide (p. 163) Arsphenamine (p. 42) Cefetrizole (p. 104) (p. 165) (p.44) Cefivitril (p. 106) Cefuracetime (p. 167) Aziocillin (p. 46) (p. 108) (p. 169) (p.48) ( p. 110) (p. 171) (p. 50) (p. 112) (p. 173) (p. 52) (p. 114) (p.175) (p. 54) (p. 116) (p. 177) (p. 56) (p. 118) (p. 179) (p. 58) (p. 120) (p. 181) (p. 60) (p. 122) (p. 183) (p. 62) (p. 124) (p. 185) Cefalogycin (p. 64) Cefoxazole (p. 126) Clofazimine (p. 187) Cefaloram (p. 66) (p. 128) (p. 189) Cefaloridine (p. 68) (p. 130) (p. 191) (p. 70) (p. 132) (p. 193) Cefaparole (p. 72) (p. 134) (p. 195) (p. 74) (p. 136) (p. 197) (p. 76) (cephradine) (p. 199) (p. 78) ( p. 138) (p. 201) (p. 80) Cefrotil (p. 141) (p. 203) (p. 82) (p. 143) Doxorubicin (p. 205) Cefcanel (p. 84) (p. 145) (p. 207) (p. 86) (p. 147) (p. 209) Cefclidine (p. 88) (p. 149) (p. 211) (p. 90) (p. 151) (p. 213) (p. 92) (p. 153) Ethambutol (p. 215) (p. 94) (p. 155) Ethionamide (p. 217) Cefedrolor (p. 96) (p. 157) (p. 219)

Computational Antibiotics

Flucloxacillin (p. 221) (p. 286) Silversulfadiazine (p. 352) (p. 223) Norfloxcin (p. 288) (p. 354) (p. 225) (p. 290) Spartfloxacin (p. 356) (p. 227) (p. 292) (p. 358) (p. 229) (p. 295) (p. 360) Geldanamycin (p. 231) Oxytetracyline (p. 297) (p. 363) (p. 233) (p. 299) (p. 366) (p. 235) (p. 301) (p. 368) (p. 237) Penicillin G (p. 303) Sulfaethizole (p. 370) Herbimycin (p. 239) Penicillin V (p. 305) (p. 372) (p. 241) (p. 307) (p. 374) Kanamycin (p. 244) (p. 309) Sulfasalazine (p. 376) Keflin (p. 246) (p. 311) Sulfisoxazole (p. 378) (p. 248) (p. 313) Torezolid (p. 380) (p. 250) (p. 315) Teflaro (Ceftaroline) (p. 382) (p. 252) (p. 317) (p. 384) (p. 254) Platensimycin (p. 320) (p. 386) (p. 256) B (p. 322) (p. 388) Mefoxin (p. 258) (p. 324) (p. 391) (p. 260) (p. 326) (p. 393) Metamide (p. 262) (p. 328) Tetracycline (p. 395) (p. 264) Pyrozinamide (p. 330) (p. 397) (p. 266) Quinupristin (p. 332) (p. 399) (p. 268) (p. 334) (p. 401) (p. 270) (p. 336) Tinidazol (p. 403) (p. 272) Rifampin (p. 338) (p. 405) Mupirocin (p. 274) (p. 340) (p. 407) (p. 276) (p. 342) (p. 409) (p. 278) (p. 344) (p. 411) (p. 280) Roxarsone (p. 346) Viomycin (p. 414) (p. 282) (p. 348) (p. 416) (p. 284) (p. 350) (p. 418)

Computational Antibiotics

Graph 1: Molar mass vs. total polar surface area (TPSA) (p. 420)

Graph 2: Dipole moment vs. total polar surface area (TPSA) (p.421)

Graph 3: Total polar surface area vs. molecular volume (p.422)

Graph 4: Total polar surface area vs. number of hydrogen bond donors (p.423)

Graph 5: Total polar surface area vs. number of hydrogen bond acceptors (p.423)

Graph 6: Total polar surface area vs. surface area (p.424)

Graph 7: Total polar surface area vs. number of rotatable bonds (p.425)

Graph 8: Total polar surface area vs. ratio of dipole to molecular volume (D/V) (p.426)

Graph 9: Total polar surface area vs. mlog P (p.427)

Graph 10: Molar mass vs. dipole moment (p.428)

Graph 11: Molar mass vs. molar volume (p.429)

Graph 12: Molar mass vs. number of hydrogen bond donors (p.430)

Graph 13: Molar mass vs. surface area (p.431)

Graph 14: Molar mass vs. number of hydrogen bond acceptors (p.432)

Graph 15: Molar mass vs. number of rotational bonds (p.432)

Graph 16: Molar mass vs. ratio of dipole to molecular volume (D/V) (p.434)

Graph 17: mlog P vs. molar mass (p.435)

Graph 18: Dipole moment vs. molecular volume (p.436)

Graph 19: Dipole moment vs. number of hydrogen bond donors (p.437)

Graph 20: Dipole moment vs. number of hydrogen bond acceptors (p.438)

Graph 21: Dipole moment vs. surface area (p.439)

Graph 22: Dipole moment vs. number of rotatable bonds (p.440)

Graph 23: Ratio of dipole moment to molecular volume (D/V) vs. number of rotational bonds (p.441

Graph 24: Number of rotatable bonds vs. mlog P (p.442)

Graph 25: Molecular volume vs. number of hydrogen bond donors (p.443)

Computational Antibiotics

Graph 26: Molecular volume vs. number of hydrogen bond acceptors (p.444)

Graph 27: Molecular volume vs. surface area (p.445)

Graph 28: Number of rotatable bonds vs. molecular volume (p.446)

Graph 29: Dipole moment vs. molecular volume (p.447)

Graph 30: Molecular volume vs. mlog P (p. 448)

Graph 31: Number of hydrogen bond donors vs. number of hydrogen bond acceptors (p. 449)

Graph 32: Number of hydrogen bond donors vs. surface area (p. 450)

Graph 33: Number of hydrogen bond donors vs. number of rotatable bonds (p. 451)

Graph 34: Ratio of dipole moment to molecular volume (D/V) vs. number of hydrogen bond donors (p. 452)

Graph 35: mlog P vs. hydrogen bonds donor (p. 453)

Graph 36: Surface area vs. number of hydrogen bond acceptors (p. 454)

Graph 37: Number of rotatable bonds vs. hydrogen bond acceptors (p. 455)

Graph 38: Dipole moment vs. number of hydrogen bond acceptors (p. 456)

Graph 39: mlog P vs. number of hydrogen bond acceptors (p. 457)

Graph 40: Number of rotatable bonds vs. surface area (p. 458)

Graph 41: Ratio of dipole to molecular volume (D/V) vs. surface area (p. 459)

Graph 42: mlog P vs. surface area (p. 460)

Graph 43: Number of rotatable bonds vs. ration of dipole to molecular volume (D/V) (p. 461)

Graph 44: Number of rotatable bonds vs. mlog P (p. 462)

Graph 45: Dipole moment vs. molecular volume (p. 463)

Computational Antibiotics

Computational Details

Each of the molecules in this compilation can be downloaded from the web site

http://antibiotics.valdosta.edu

Using the password “antibiotic” (no quotes).

This project was conducted using Spartan Cluster (Wavefunction) software. Structural parameters were calculated using Semi empirical PM3 (neutral). Additional ions that might be present in the actual pharmaceutical agents (sulfate, chloride, etc.) were not included in the structures or calculations.

Molinspiration (http://www.molinspiration.com/services/properties.html) was used to calculate parameters such as number of rotatable bonds, logP (water-octanol partition coefficient), TPSA, etc. These are parameters linked to Lipinski’s Rules.

Each page contains some additional information about the molecules including different names, cell line and clinical studies and some review papers that may be available on the web.

These are by no means to be considered a complete list of citations.

This book and website are the result of a class project in a CHEM4920 class entitled

“Antibiotics”.

Note the page numbers are approximate as the *.pdf compilation can shift the files while combining into a single document.

Computational Antibiotics

ACKNOWLEDGEMENTS

We would like to thank several divisions and individuals at Valdosta State University

(www.valdosta.edu, Valdosta, Ga.). The Information Technology Division is thanked for maintaining the chemistry department computer lab and cluster where much of this work was performed. Also, the installation and maintenance of the research version of Spartan (Wavefunction, Calif.) was performed by the VSU-IT group. We are especially thankful to David Pierce, Annon Beepath, Dwayne Trouille, Gary

Kuhlmann, Ike Barton, and Joe Newton. Mr. Ben Li of the VSU library is thanked for his help with posting the antibiotic molecular structures to the web.

The chemistry department, led by Dr. Jim Baxter, is also thanked for their help with software and hardware. We have a special shout out to Melissa Moore-Nolley in the chemistry department for her kindness and problem solving skills in dealing with logistical problems and humanity! Kaci Starling might be the greatest student assistant of all time and is thanked for all her work. This project is supported by the VSU Academic Equipment Fund, the Deans office (Dr. Connie Richards) and the VSU QEP Project led by Dr. Jim "GB" LaPlant and Dr. Michael Black. The VSU Faculty Research and Scholarship fund, in its various forms over the years, has been of great assistance. The VSU Library and Media Center including but not limited to Mr. Rex DeVane and Ms. Denise Montgomery, are thanked for all of their direct and indirect assistance with this project. We, both student and faculty authors, would like to thank various faculty that have given us insight to microbes, structures and biochemical over the years including the late Dr. Linda Chamberlin, Dr. Jenifer Turco, Dr. Jim Nienow,

Dr. John Elder, Dr. Donna Gosnell, Dr. Yakov Woldman, Dr. Lynn Wood, Dr. John Barbas, Dr. Linda

DeLaGarza, Dr. Tolu Salami, Dr. Jim Baxter, Dr. Jenny Vu, Dr. Art Jonas, Dr. Ligia Focsan, Dr. Dean

Duncan, Dr. Al Fuciarelli, Dr. Jesse Spencer, Dr. Betty Derrick, Dr. Lyn Noble, Dr. Warren Fiskus and

Dr. Dave Newman.

Eugene Rowell would like to thank the Honors Program (Dr. Mike Savoie) for allowing him to conduct an Honors Option for this class. Chelsie Northcutt is thankful to the National Science

Foundation – Noyce Scholar Program (PI, Dr. Brian Gerber) for her support.

Computational Antibiotics

Several individuals and groups have helped us over the years develop our work first in natural products than in antibiotics. We would like to thank Dr. Jim Boyce of the NIH Infectious Diseases section for allowing our compounds to be tested (Tb). This research inspired additional work with antibiotics.

Dr. Dennis Phillips of the University of Georgia Chemistry Department and Dr. Greg Wylie, formerly of

UGa and currently of Texas A&M are thanked for their many collaborative efforts. Dr. Alan Marshall and the FT-ICR group at the National High Field Magnet Lab (Tallahassee, Florida) are thanked for access to their equipment and their expertise over the years.

We would like to thank Wavefunction and Molinspiration staff for making their products user friendly and available. We would also like to thank Dr. Eric Strong of Stanford University for his on-line antibiotic lectures. This high quality, succinct work helped the class gain a broad view of the topic.

Computational Antibiotics

Dedications

• Brandon Rush would like to dedicate the contribution he put forth in this book to his grandmother Jeannette M. Rush. With her passing away recently, he would like his final dedication to be for her.

• Edwin Saint-Louis: I dedicate this book to Dr. Manning, all of my antibiotics classmates, friends, and family.

• Chelsie Northcutt, I would like to dedicate my contributions to this book to the following: God, my family and friends, and last, but certainly not least, Dr. Manning. Thank you for all of your help and support!

• Chandler Massey, I would like to dedicate my contribution to this book to my classmates of Dr. Manning’s antibiotic class.

• Somuayiro Nwokike: I would like to dedicate my contribution in this book to my family, friends, and classmates for their love and support.

• I (Jared Harris) want to dedicate my contributions toward this book to the VSU Chemistry, my fellow classmates, and Dr. Manning for making this possible.

• Amy Vardeman would like to dedicate her contribution to this book to Eugene Rowell III, who has made her college experience one that she will never forget.

• Andrew DeLong dedicates his work on this book to his family and friends for their support and inspiration.

• Brit Larcart to Joshua Palmer, thank you for revealing potential I could not see in myself.

• Pratikkumar P. Patel, I am both thankful and blessed to be a part of Valdosta State University and it has been my privilege to work under the guidance of Dr. Manning and Dr. Abadi. I would like to dedicate my contribution to this book to my family and friends who were always there for me.

• Harsh Patel; I would like to dedicate this book to my cousin for inspiring me to choose a field to learn about various drugs, and going into the field of Pharmacy.

• Eugene Rowell; I would like to dedicate my contribution to this book to Amy Vardeman for always having a smiling face even on the bad days.

Computational Antibiotics

• Felicia Woods, I would like to dedicate this book to my parents, Herman and Ruby Woods, for their love and support and for always believing in me.

• Oscar Amos Otieno would like to dedicate this book to Dr. Thomas Manning for being a good adviser for the past four and half years.

• Brandon Rush would like to dedicate the contribution he put forth in this book to his Grandmother. She has always supported and been there for him. With her passing away recently, he would like his final dedication to be for her.

• Prof. Tom Manning would like to thank his science and math teachers over the years including Ms. Demasi from St. Joseph. St. Thomas (Pleasant Plains, Staten Island); Mr. Romani, Mr. Soma, Br. Bray and Mr. Eisenberg from Monsignor Farrell, Dr. Deavor, Dr. Kinard, Dr. Asleson, Dr. Heldrich, Dr. Doig, Dr. Metz, and Ms. Martin from the College of Charleston (SC) chemistry department, Dr. Greg Wilson my the BCIM Division at MUSC, Dr. Geoff Coleman formerly of the University of Alabama, Dr. Jim Winefordner from University of Florida (grad school), Dr. Byron Palmer and Mr. Doug Hof from Los Alamos National Lab, and Dr. Greg Choppin from Florida State University (post doc). He would especially like to thank his parents who were his most influential teachers.

Computational Antibiotics

Introduction to Antibiotics

The discovery of penicillin 86 years ago, by Alexander Fleming, paved the way for the development and treatment of infection in health care. The discovery, isolation and mass production of penicillin saved millions of lives during World War II, and allowed for the discovery and production of other drugs, which were classed as antibiotic drugs. The discovery of antibiotics introduced new insight into the treatment of infections and venereal diseases; drugs that destroyed without harming the human body.(i,ii,iii,iv,v)

Twelve years after the discovery of penicillin, the drug was commercialized and within four years, cases of penicillin resistant strains of aureus became evident.(vi,vii) The initial stages of resistant strains were addressed by administering alternative antibiotic drugs such as erythromycin, vancomycin, and novobicin for treatment. At the same time, a need to understand how and why the resistant strains began became a necessity. In 1945, St. Jude’s hospital showed that the sensitivity of penicillin was usually temporary and generally decreases over a period of 6-12 months. Due to the unpredictably hypersensitivity of penicillin, it was recommended that patients with a history of sensitivity to penicillin be administered alternative drugs.(viii)

As early as the 1960’s, studies showed that the production of penicillinase was responsible for the resistant strains of S. aureus. Penicillinase exerts its action by hydrolyzing penicillin at the β-lactam ring preventing the drug from reaching its target site.(ix) Aside from substituting alternative antibiotics for treatment, much research was invested into creating semi- synthetic penicillin drugs such as phenethicillin, methicillin and other penicillin derivatives such as penicillin G, penicillin V, and penicillin N.(x) With the discovery of methicillin and phenethicillin, studies showed that the bioactivity of phenethicillin was only slightly greater than that of penicillin G; and that methicillin is greater than that of phenethicillin, however penicillin still inhibited bacterial growth at lower concentrations than either drug.(xi,xii) Within two years of methicillin distribution, resistant strains to the drug occurred resulting in MRSA (methicillin- resistant ). Studies have shown that MRSA occurs due to the acquisition of the mecA gene which encodes a unique penicillin-binding protein located at the 2’ or 2a position. This decreases the affinity for β-lactam and catalyses synthesis.(xiii,xiv,xv,xvi)

Computational Antibiotics

Within the past 55 years, the urgency for novel antibiotic drugs has greatly increased; as a result, drugs are now being screened for anti-MRSA activity.(xvii,xviii) Recent studies have shown that marine actinomycete species have shown effective against anti-MRSA. A study of etamycin against MRSA, showed that etamycin alone worked more rapidly within the first 6 hrs, in comparison to vancomycin, however the drug wasn’t as effective as vancomycin in the 24 hr assay.(xix,xx)

The increase of antibiotic resistance is believed to be associated with the misuse of the drug and socio-economic factors. Factors such as poor hygiene, lack of education and misuse of antibiotics in both health care and agriculture only begins to explain how quickly resistance strains began.(xxi,xxii) In health care, a major issue is administering antibiotics before identifying the source of the infection. In agriculture, a major issue is administering antibiotics to farming cattle, whose waste is then used to fertilize field. The reabsorption of antibiotics in food thus contributes to the increase in bacterial resistance over the past 20 years.(xxiii,xxiv)

Despite the current need for anti-resistant antibiotics, there has been a great decline in the development of new drugs. The short term administration of such drugs and the high risk of resistant strains, high cost and FDA regulations have caused many companies to abandon or reduce the research and development of antibiotic drugs.(xxv,xxvi) Introducing new compounds to the market can take an average of 10-12 years costing companies $800-$2000 million dollars per drug. With the lifetime of the drugs on the market averaging at 8-10 years, such risks have discouraged companies from further research.(xxvii,xxviii) As a result, companies are addressing the issue of resistant strains by prescribing drugs as combinational therapy, readdressing drug design for known drugs and focusing on natural product extraction for the isolation of new antibiotic drugs.(xxix,xxx,xxxi,xxxii,xxxiii,xxxiv) Fursidic acid and are examples of two old antibiotic drugs that initially showed great , however resistance to both drugs quickly developed. Combination therapy of fursidic acid and fosfomycin, is one example of many that have been revisited. Initial studies have shown that fusidic acid and fosfomycin have significant activity against most strains of MRSA. The low toxicity of fosfomycin and efficacy of fusidic acid shows that the combination of both drugs exhibit activity at lower concentration values than either drug alone.(xxxv)

Computational Antibiotics

New drugs such as Fidaxomicin, Bedaquiline, platensimycin, platencin and surotomycin were approved by the FDA within the past 4 years, with only twenty new antibiotic drugs currently in phase II/III clinical trials since 2000.(xxxvi,xxxvii,xxxviii,xxxix) Fidaxomicin has showed fewer recurrence of Clostridium difficile in comparison to patients treated with vancomycin by 10.6%. This drug therefore offers promise to treating patients by limiting the use of the drug solely to patients with an increased risk of recurrence.(xl)

The revolutionary impact that the discovery of antibiotic drugs brought to medicine and the financial attribution to the , has greatly benefited many people. Despite its application to health care and current issues of resistant strains, there has been few and extremely rare cases where antibiotic drugs have posed detrimental to patients. Antibiotic drugs such as chloramphenicol, cyclosporine, nitrofurantion, meropenem, and albendazole have each reported rare cases of side effects, some of which resulted in patient death.(xli,xlii,xliii,xliv,xlv,xlvi)

For example, meropenem, a β-lactam drug, is widely used for the treatment of meningitis and . A very rare case was reported of meropenem induced pancytopenia and sepsis three days after taking the drug, resulting in death.(xlvii,xlviii)

Chloramphenicol, trade name chloromycetin, showed a greater bioactivity against a wider variety of bacteria than penicillin. The drug was used to treat psittacosis, rocky mountain , typhoid and paratyphoid fever, and rickettsiae, however by 1952 several cases were reported of patients who developed severe anemia.(xlix,l) Another case was reported of a patient who developed hepatitis after treated with chloramphenicol, whose liver function normalized within 10 months of having stopping treatment.(li)

Nitrofurantoin is widely used for the treatment of short and long term urinary tract infections; however, since 1961 numerous cases of hepatotoxicity have been reported due to nitrofurantoin. Patients generally present symptoms within a few days to weeks after their initial intake of the drug. Patients with chronic forms of nitrofurantoin hepatotoxicity generally present symptoms within 6 months to several years after their initial intake.(lii,liii)

Even with the minimal dangers associated with antibiotic drugs, overall use of antibiotics have been a success, however the production of antibiotics has greatly diminished over the past

Computational Antibiotics

30 years. Since the early 1980’s, the number of antibiotic drugs approved by the FDA (food and drug administration) has greatly decreased. To overcome this, the FDA modified their testing regulations of drugs by decreasing developmental time which would decrease production expenses. Having reduced the developmental time by 5 years, 61 antibiotic drugs were approved by the FDA in the 1980s, 26 of which were withdrawn between 1980 and 1999 for health and safety reasons. These drugs were primarily from the cephalosporin and fluoroquinolone family of antibiotics.(liv) with the rise of more resistant bacteria, it is believed that until a drug can be developed to eradicate MRSA, several socio economics steps will need to be implemented to reduce the percentage of MRSA worldwide.

i Wrong, N. W., Smith, R. C., Hudson, A. L., Hair, H. C. 1951. The treatment of pyogenic skin infections with bacitracin ointment. Canadian Medical Association Journal, 64, 395-397.

ii Johnson, B. A., Anker, H., Meleney, F. L.1945. Bacitracin: a new antibiotic produced by a member of the B.

subtilis group. Science, 102, 376-377.

iii Finland, M. 1978. Future clinical studies for the national Institute of and Infectious Diseases. Annals of

Internal Medicine, 89 (2), 849-853.

iv Demain, A. L., Sanchez, S. 2009. Microbial drug discovery: 80 years of progress. The Journal of Antibiotics, 62,

5-16.

v Kardos, N., Demain, A. L. 2011. Penicillin: the medicine with the greatest impact on therapeutic outcomes.

Applied microbiology and biotechnology, 92, 677-687.

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vi Rammelkamp, C. H., Maxon, T. 1942. Resistance of staphylococcus aureus to the action of penicillin.

Proceedings of the Society for Experimental Biology and Medicine, 51, 386-389.

vii Coles, N. W., Gross, B. 1965. The induced formation of penicillinase in staphylococcus aureus. The Australian

Journal of Experimental Biology and Medical Science, 43, 725-736.

viii Grieco, M. H., Dubin, M. R., Robinson, J. I., Schwartz, M. J. 1964. Penicillin hypersensitivity in patients with

bacterial endocarditis. Annals of Internal Medicine, 60, 2, 204-216.

ix Graham, D. C., Routley, T. C., Dickinson, G. T., Randall, R. L. 1960. Resistant staphylococci and the new

synthetic . Canadian Medical Association Journal, 83, 822-823.

x Ing, H. R. 1961. Semi-synthetic penicillins. Proceeding Chemical Society, 1, 6.

xi Fekety Jr., F. R., Cluff. L. E. 1962. Studies on the antibiotic therapy of serious staphylococcal infections. Annals

of Internal Medicine, 56, 2, 198-205.

xii Branch, A., Rodger, K. C., Lee, R. W., Power, E. E. 1960. Clinical and laboratory experiences with a new synthetic penicillin- - 2, 6-dimethoxyphenyl penicillin. Canadian Med Ass Journal, 83, 991-996.

xiii Tsubakishita, S., Kuwahara-Aiai, K., Sasaki, T. 2010. Origin and molecular evolution of the determinant of methicillin resistance in Staphylococci. Antimicrobial agents and chemotherapy, 54(10), 4352-4359.

xiv Lambert, P. A. 2005. Bacterial resistance to antibiotics: modified target sites. Advanced Drug Delivery Reviews,

57(10), 1471-1485.

xv Couto, I., de Lencastre, H., Serverina, E., Kloos, W., Webster, J. A., Hubner, R. J., Santos Sanches, I., Tomasz, A.

1996. Ubiquitous presence of a mecA homologue in natural isolates of staphylococcus sciuri. Microbial Drug

Resistance, 2(4), 377-391.

xvi Chambers, H. F. 1997. Methicillin resistance in staphylococci: molecular and biochemical basis and clinical

implications. Clinical Microbiology Reviews, 10, 781-791.

xvii Moellering Jr., R. 2012. MRSA: the first half century. The J. of Antimicrobial Chemotherapy, 67, 4-11.

xviii Moellering Jr., R. 2006. Vancomycin: A 50 year Reassessment. Clinical Infectious Dis., 42 (1), S3-4.

xix Haste, N. M., Perera, V. R., Maloney, K. N., Tran, D. N., Jensen, P., Fenical, W., Nizet, V., Hensler, M. E. 2010.

Activity of the antibiotic etamycin against methicillin-resistant Staphylococcus aureus. The Journal of

Antibiotics, 63, 219-224.

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xx Hughes, C. C., Prieto-Davo, A., Jensen, P. R., Fenical, W. 2008. The marinopyrroles, antibiotics of an unprecedented structure class from a marine sp.. Organic Letters, 10, 629-631.

xxi Brinsley, K. J., Sinkowitz-Cochran, R. I., Cardo, D. M., CDC campaign to prevent team.

2005. Assessing motivation for physicians to prevent antimicrobial resistance in hospitalized children using the health belief model as a framework. American Journal of Infection Control, 33 (3), 175-181.

xxii Ilic, K., Jakovljevic, E., Skodric-Trifunovic, V. 2012. Social-economic factors and irrational antibiotic use as reasons for antibiotic resistance of bacteria causing common childhood infections in primary healthcare. European

Journal of Pediatrics, 171, 767-777.

xxiii Levy, S. B. 1998. Multidrug resistance – a sign of the timer. The New England Journal of Medicine, 1998, 338

(19), 1376-1378.

xxiv Levy, S. B. 2001. Antibiotic resistance: consequences of inaction. Clinical Infectious Diseases, 33 (3), S124-

129.

xxv Wright, G. D. 2013. Q&A: Antibiotic resistance: what more do we know and what more can we do? BMC

Biology, 11, 51.

xxvi Gal, K. 1965. Combined antibiotic therapy. Canadian Medical Association Journal, 93, 844-847.

xxvii Katz, M. L., Muller, L. V., Polyakov, M., Weinstock, S. F. 2006. Where all the antibiotic patents gone? Nature

Biotechnology, 24, 1529-31.

xxviii Quinn, R. 2013. Rethinking antibiotic research and development: World War II and penicillin collaborative.

American Journal of Public Health, 103 (3), 426-434.

xxix Gould, I. M., Bal, A. M. 2013. New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence, 4 (2), 185-191.

xxx Berdy, J. 2012. Thoughts and facts about antibiotics: Where we are now and where we are heading. The Journal

of Antibiotics, 65, 385-395.

xxxi Ikeda, S., Hanaki, H., Yanagisawa, C., Ikeda-Dantsuji, Y., Matsui, H., Iwatsuki, M., Shiomi, K., Nakae, T.,

Sunakawa, K., Omura, S. 2010. Identification of the active component that induces vancomycin resistance in

MRSA. The Journal of Antibiotics, 53, 533-538.

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xxxii Wright, K. L. 2011. Antibiotic adjuvants: multicomponent anti-infective strategies. Expert Reviews in

Molecular Medicine, 13, 5.

xxxiii Yahav, D., Farbman, L., Leibovici, L., Paul, M. 2012. : new on an old antibiotic. Clinical Microbiology

and Infection, 18 (1), 18-28.

xxxiv Zervosen, A., Sanvage, E., Frere, J. M., Charlier, P., Luxen, A. 2012. Development of new drugs for an old

target – the penicillin binding proteins. Molecules, 17, 12478-12505.

xxxv Yu, X-H., Song, X-J., Cai, Y., Liang, B-B., Lin, D-F., Wang, R. 2010. In vitro activity of two old antibiotics against clinical isolated of methicillin-resistant Staphylococcus aureus. The Journal of Antibiotics, 2010, 63, 657-

659.

xxxvi Martens, E., Demain, A. L. 2011. Platensimycin and platencin: promising antibiotics for future application in

human medicine. The Journal of Antibiotics, 64, 705-710.

xxxvii Butler, M. S., Cooper, M. A. 2011. Antibiotics in the clinical pipeline in 2011. The Journal of Antibiotics, 64,

413-425.

xxxviii Banskota, A. H., Aouidate, M., Sorensen, D., Ibrahim, A., Piraee, M., Zazpoulos, E., Alarco, A-M., Gourdeau,

H., Mellon, C. 2009. TLN-05220, TLN-05223, new Echinosporamicin-type antibiotics, and proposed revision of the structure of bravomicins. The Journal of Antibiotics, 62, 565-570.

xxxix Donadio, S., Maffioli, S., Monciardini, P., Sosio, M., Jabes, D. 2010. Antibiotic discovery in the twenty-first

century: current trends and future perspectives. The Journal of Antibiotics, 63, 423-430.

xl Johnson, A. P., Wilcox, M. H. 2012. Fidaxomicin: a new option for the treatment of Clostridium difficile infection. The Journal of Antimicrobial Chemotherapy, 67, 2788-2792.

xli Sergin, G., Elbek, O., Balantekin, C., Meteoglu, I., Culhaci, N. 2012. Acute respiratory distress syndrome and hepatotoxicity associated with single dose nitrofurantoin use. Hindawi publishing corporation, 465389.

xlii Sakaan, S. A., Twilla, J. D., Usery, J. B., Winton, J. C., Self, T. H. 2014. Nitrofrantoin-induced hepatotoxicity: a rare yet serious complication. Southern Medical Journal, 107 (2), 107-113.

xliii Arber, C., Buser, A., Heim, D., Gratwohi, A., Tichelli, A., Passweg, J, R. 2006. Cyclosporine-responsive thrombocytopenia in a patient with chloramphenicol-associated myelodsplastic syndrome. European Journal of

Haematology, 76, 255-257.

Computational Antibiotics

xliv Marin Zuluaga, J. I., Marin Castro, A. E., Perez Cadavid, J. C., Restrepo Gutierrez, J. C. 2013. Albendazole-

induced granulomatous hepatitis: a case report. Journal of Medical Case Reports, 7, 201.

xlv Grill, M. F., Maganti, R. K. 2011. Neurotoxic effects associated with antibiotic use: management considerations.

British Journal of Clinical Pharmacology, 72 (3), 381-393.

xlvi Walker, A. S. CPT, Causey, M. W. CPT, Sebesta, J. A. CPT. 2012. Cefazolin-induced neutropenia and

thrombocytopenia following trauma: a case report. Military Medicine, 177 (3), 352-354.

xlvii Baldwin, C. M., Lyseng-Williamson, K. A., Keam, S. J. 2008. Meropenem: a review of its use in the treatment of serious bacterial infections. Drugs, 68 (6), 803-838.

xlviii Erden, M., Guican, E., Bilen, A., Bilen, Y., Uyanik, A., Keles. M. 2013. Pancytopenia and sepsis due to meropenem: a case report. Tropical Journal of Pharmaceutical Research, 12 (1), 127-129.

xlix Petersdorf, S. H., Raisys, V. A., Opheim, K. E. 1979. Microscale method for liquid chromatographic

determination of chloramphenicol in serum. Clinical Chemistry, 25, 1300-1302.

l Anadon, A. 1985. Standard residue regulations for chloramphenicol in Spain. Annals of Veterinary Research, 16,

149-153.

li Doshi, B., Sarkar, S. 2009. Topical administration of chloramphenicol can induce acute hepatitis. British Medical

Journal, 338, 2699

lii Sakaan, S. A., Twilla, J. D., Usery, J. B., Winton, J. C., Self, T. H. 2014. Nitrofurantoin-induced hepatotoxicity: a rare yet serious complication. Southern Medical Journal, 107 (2), 107-113.

liii Ernaelsteen, D., Williams, R. 1961. Jaundice due to nitrofurantoin. Gastroenterology, 41, 590-593.

liv Outterson, K., Powers, J. H., Seoane-Vasquez, E. 2010, Approval and withdrawal of new antibiotics and other antiinfectives in the US., 1980-2009. Journal of Law, Medicine & Ethics, 688-696.

Computational Antibiotics

Penicillin’s

Penicillin is a group of antibiotics derived from the Penicillium fungi. Penicillins are β- lactam antibiotics that are used for the treatment of gram positive bacterial infections. β-Lactam

antibiotics inhibit the formation of cross-links in the bacterial cell wall.(1) This is

achieved by the binding of the four membered ring (β-Lactam) to .(2) The structure of all penicillin’s contains a “R” group which differs in each penicillin. Penicillin was first discovered in 1874 by William Roberts, and later further analyzed by Alexander Flemming.(3) These

antibiotics were among the first to prove effective against diseases such as syphilis and infections

caused by staphylococci and streptococci. Some trade names for penicillin are Amoxil,

Cloxapen, Pfizerpen.

Today, only a select few penicillin drugs such as amoxicillin and penicillin G are still

used, due to the increased resistance strains of many bacteria. In New York, hospitals have

stopped testing for susceptibility to penicillin, because they believe that many strains that were

once susceptible are now extinct.(4) As a result, other forms of antibiotic treatments may be found in combination with other drugs such as Amoxicillin/clavulanate and Piperacillin/ combination to try to overcome the resistance.(5)

1 Blumberg, P. M., Strominger, J. L. 1974. Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes. Bacteriological Reviews, 38(3), 291–335. 2 Park, J. T., and Strominger, J. L. 1957. Mode of Action of Penicillin: Biochemical Basis for the Mechanism of Action of Penicillin and for Its Selective Toxicity. Science, 3238 (1957), 99-101. 3 Grossman, C. M. 2008. The First Use of Penicillin in the United States. Annals of Internal Medicine, 149(2), 135. 4 Crane, J. K. 2014. Resurgence of penicillin-susceptible Staphylococcus aureus at a hospital in New York State, USA The Journal of Antimicrobial Chemotherapy, 69, 280-281. 5 Caron, F., Ducrotte, P., Lerebours, E., Colin, R., Humbert, G., Denis, P. 1991. Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings. Antimicrobial agents and chemotherapy, 35(6), 1085-1088 Carbapenems

Carbapenems are a group of antibiotics that belong to the class β-lactam antibiotics. The development of β-lactamase bacteria during the 1960’s marked the birth of class β-lactam antibiotics. This form of bacteria had significantly reduced the effectiveness of penicillin.(6)

Carbapenems have a structure similar to that of penicillin, which can be referred to as .

The carbopenem backbone is composed of a four and five membered ring that share a nitrogen

atom, which serves as a general structure to which three alkyl groups are added.

Carbapenems are effective against gram-positive, gram-negative, and anaerobic

bacteria.(6,7) There are four FDA approved antibiotic drugs currently available in the

United States: Imipenem, Doripenem, Meropenem, and Ertapenem.(7) Primaxin and Merrem are

used as a last resort for some extreme bacterial infections with resistant strain for Escherichia

coli (E. coli) and Klebsiella pneumonia.(6) Carbapenems are mainly used to treat bacterial

infections that are acquired in a hospital setting.(6)

Currently there is a concern for recent isolated cases involving New Delhi metallo-β- lactamase, an NDM-1 strain bacterium which has shown resistance to carbapenems. The strain is associated with E. coli bacteria. Research regarding NDM-1 resistance to carbapenems is still underway, however there is some evidence varying the minimal inhibitory concentrations of the carbapenems.(8)

6 Papp-Wallace K. M., Endimiani A., Taracila M. A., Bonomo R. A. 2011. Carbapenems: past, present, and future. Antimicrobial agents and chemotherapy, 55 4943–4960. 7 Miller, A. D., Ball, A. M., Bookstaver, P. B., Bennett, C. L. 2011. Epileptogenic Potential of Carbapenem Agents: Mechanism of Action, Seizure Rates, and Clinical Considerations. Pharmacotherapy, 31(4), 408-423. 8 Wiskirchen, D. E., Nordmann, P., Crandon, J. L., Nicolau, D. P. 2013. Efficacy of Humanized Carbapenem Exposures Against New Delhi Metallo-Beta-Lactamase (NDM-1)-Producing In A Murine Infection Model. Antimicrobial Agents and Chemotherapy, 57(8), 3936-3940. Oxazolidines

Oxazolidines are pentagonal ringed compounds that consist of three carbons, an oxygen

and a NH bond in the 1 and 3 positions. Oxazolidines have been synthesized for , fungicides, herbicides, and mosquito repellents.(9) There are several derivatives of oxazolides

namely: isoxazolidines, bisoxazolidines, oxazolidinediones, and oxazolidinone; however, the

most common derivative is the oxazolidinone antibiotics. This group of antibiotics is involved in

protein synthesis inhibition, which interrupts the early step of binding of t-RNA to the

ribosome.(10)

Linezolid was the first antibiotic discovered from the oxazolidinone group, which inhibits

the growth of a wide variety of gram-positive pathogens.(11) Oxazolidinones are still being used

for the treatment of diseases such as nosocomial pneumonia, complicated skin and skin-structure

infections. These diseases are caused by methicillin-sensitive or methicillin-resistant

Staphylococcus aureus, and vancomycin-resistant faecium infections.(12) The trade

names associated with oxazolidines are zyvox, zyvoxid or linezolid.

9 Moloney G., Iskander M., Craik D. 2010. Stability studies of oxazolidine-based compounds using 1H NMR spectroscopy. Journal of Pharmaceutical Sciences, 99(8), 3362-3371. 10 Shinabarger, D. 1999. Mechanism of action of the oxazolidinone antibacterial agents. Expert opinion on investigational drugs, 8(8), 1195-1202. 11 Ford, C., Zurenko, G., Barbachyn, M. 2001. The Discovery of Linezolid, the First Oxazolidinone Antibacterial Agent Current Drug Targets - Infectious Disorders, 1(2), 181. 12 Fung H., Kirschenbaum H., Ojofeitimi B. 2001. Linezolid: an oxazolidinone antimicrobial agent. US National Library of Medicine National Institutes of Health. 23(3), 356-91.

Rifamycin The , trade name ridafin, belong to the family of ansamycin antibiotics, named

because of their basket-like molecular architecture comprising of an aromatic moiety bridged at

nonadjacent positions by an aliphatic chain.(13) They manufacture, either in its natural or artificial

state, by the bacteria Amycolatopsis Mediterranei. Rifamycins were first isolated by Grazia

Beretta and Pinhas Margalith, in 1957 from a culture of Streptomyces Mediterranei.(14) Seven

Rifamycins were discovered named Rifamycin A, B, C, D, E, S, and SV. Rifamycin B, which was first introduced, was granted a patent in September 1964.(14) Rifamycins are mainly used

to treat tuberculosis, leprosy, and mycobacteria.(13) They are gram-positive and gram-negative bacteria that work by inhibiting the RNA in bacteria.(14) Recent studies are

looking at the applications of Rifamycin for the treatment of tuberculosis in HIV-infected

patients.(15) Rifamycin has also shown to be an effective drug for the treatment and prevention

of travelers’ due to -predominant bacterial pathogens.(16)

13 Floss, H. G., Yu, T-W. 2005. Rifamycin mode of action, resistance, and biosynthesis. Chemical Reviews, 105(2), 621-632. 14 http://www.rightdiagnosis.com/medical/rifamycin.html February 20, 2014 15 Weiner, M., Benator, D., Burman, W., Peloquin, C. A., Khan, A., Vernon, A., Jones, B., Silva-Trigo, C., Zhao, Z., Hodge, T. 2005. Association between acquired rifamycin resistance and the of rifabutin and - soniazid among patients with HIV and tuberculosis. Clinical Infectious Diseases, 40(10), 1481-1491. 16 Gerard, L., Garey, K. W., DuPont, H. L. 2005. Rifaximin a nonabsorable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert review of anti-infective therapy, 3(2), 201-211 Lincosamides

Lincosamides, trade names daclin and cleocin, are a class of antibiotics that prevent bacteria from replicating, by interfering during protein synthesis. Lincosamides bind to the 50S subunit of bacterial ribosomes, which causes early dissociation of the peptidyl-tRNA from the ribosome.(17) Resistance to lincosamides are due to methylation of the binding site.(18)

Lincomycin was the first lincosamide discovered in 1962, which was isolated from Streptomyces lincolnensis found in a soil sample.(19) This class of antibiotics is normally used to treat staphylococci and streptococci bacterium.(20)

Clindamycin, a derivative of lincomycin was found to have better microbial bacteria, and lincomycin now has limited use.(21) Clindamycin is used to treat anaerobic infections, and is now being used to treat toxic infections involving streptococci, community-associated methicillin- resistant Staphylococcus aureus (CA-MRSA), Pneumocystis jirovecii pneumonia, and is being used as an acne treatment when paired with benzoyl peroxide.(22)

17 Tenson, T., Lovmar, M., Ehrenberg, M. 2003. The Mechanism of Action of , Lincosamides and Streptogramin B Revealthe Nascent Peptide Exit Path in the Ribosome. Journal of Molecular Biology, 330(5), 1005–1014. 18 Leclercq, R. 2002. Mechanisms of Resistance to Macrolides and Lincosamides: Nature of Resistance Elements and Clinical Implications. Clinical Infectious Diseases, 34(4), 482-492. 19 Zhang, H., Schmidt, H., Piepersberg, W. 1992. Molecular cloning and characterization of two lincomycin-resistance genes 1MRA and 1MRB from Streptomyces lincoinensis. Molecular microbiology, 6(15), 2147-2157. 20 Watanakunakorn, C. 1976. Clindamycin therapy of Staphylococcus aureus endocarditis: clinical relapse and development of resistance to clindamycin, lincomycin and erythromycin. The American Journal of Medicine, 60, 419-25. 21 Péchère, J. 1999. Current and future management of infections due to methicillin-resistant staphylococci infections: the role of quinupristin/dalfopristin. The Journal of Antimicrobial Chemotherapy, 44, 11-18. 22 Cunliffe W., Holland K., Bojar R., Levy S. 2002. A randomized, double-blind comparison of a clindamycin phosphate/benzoyl peroxide gel formulation and a matching clindamycin gel with respect to microbiologic activity and clinical efficacy in the topical treatment of acne vulgaris. Clinical Therapeutics, 24 (7), 1117–33. Quinolones

In the early 1960’s the first quinolone, Nalidixic acid, was discovered during the

synthesis of quinine, as an impurity during the isolation process. Nalidixic acid had noticeable

antimicrobial properties; the discovery of these properties was followed by decades of research

and over 10,000 derivatives of this antibiotic. (23) Quinolones affect bacterial cells by preventing

DNA from unwinding and duplicating.(24) Quinolones have been used to treat a wide range of infections including , systemic tissue infections, and respiratory infections.(23) The molecular structure of the quinolones compounds is easily manipulated, therefore modifying its activity and structure explains the thousands of derivatives. For this reason, there have been five generations of drugs that have been developed.

Quinolone derivatives are currently being studied for the treatment of malaria and MRSA,

although development of resistance is a concern.(25) Common drugs from this family include

Ciproflaxin, Levaquin, and Trovan. These drugs are from the second, third, and fourth

generations of quinolones, respectively.(24)

23 Andersson, M. I., MacGowan, A. P. 2003. Development of the quinolones. Journal of Antimicrobial Chemotherapy, 51(1), 1– 11. 24 Oliphant, C. M., Green, G. M. 2002. Quinolones: A Comprehensive Review. American Family Physician, 65(3). 25 Cross, R. M. , Namelikonda, N. K., Mutka, T. S., Luong, L., Kyle, D. E., Manetsch, R. 2011. Synthesis, Antimalarial Activity, and Structure−Activity Relationshipof 7-(2-Phenoxyethoxy)-4(1H)-quinolones. Journal of Medicinal Chemistry, 54, 8321−8327. Polypeptides antibiotics

Polypeptides antibiotics are a class of antibiotics that have activity against Gram-negative

bacilli by disrupting the membrane which contain non-protein polypeptide chains. Examples include bacitracin, colistin, , and actinimycin-D. Actinomycin D (Act D) also known as Cosmegen, is a well-known clinical antitumor drug that has been used for the treatment of some highly malignant tumors; however, the clinical application are limited due to its extreme cytotoxicity.(26)

Polymyxin B (PMX-B) trade name Polytrim, is a polycationic antibiotic known to bind

the lipid-A portion of endotoxin; a cell wall component exclusively found in gram-negative

bacteria (GNB).(27) It alters bacterial outer membrane permeability by binding to a negatively

charged site in the lipopolysaccharide layer, resulting in a destabilized outer membrane. Colistin

or Coly-micynm is used for the treatment of pneumonia associated with multidrug- resistant

Acinetobacter baumannii and aeruginosa bacterium.

Despite its use, the best route of administration and dosage is not known.(28) The peptide

antibiotic bacitracin is widely used as an inhibitor of protein disulfide isomerase (PDI) to

demonstrate the role of the protein-folding catalyst in a variety of molecular pathways.

Commercial bacitracin is a mixture of at least 22 structurally related peptides. The inhibitory

activity of individual bacitracin analogs on PDI is unknown.(29)

26 Chen, Y., Liu, J., Yuan, B., Cao, C., Qin, S., Cao, X., Guangkai Bian, Wang, Z., Jiang, J. 2013. Methylated actinomycin D, a novel actinomycin D analog induces apoptosis in HepG2 cells through Fas- and mitochondria-mediated pathways. Molecular Carcinogenesis, 52(12), 983-996. 27 Ruberto, F. F., Pugliese, F. F., D’Alio, A. A., Martelli, S. S., Bruno, K. K., Marcellino, V. V., Pietropaoli, P. P. 2007. Clinical Effects of Use Fixed on Fibers in Liver Transplant Patients With Severe Sepsis or Septic Shock. Transplantation Proceedings, 39(6), 1953-1955 28 Choi, H., Kim, Y., Kim, H., & Uh, Y. 2014. Inhaled colistin for treatment of pneumonia due to colistin-only-susceptible Acinetobacter baumannii. Yonsei Medical Journal, 55(1), 118-125. 29 Dickerhof, N., Kleffmann, T., Jack, R., & McCormick, S. 2011. Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free in the substrate-binding domain. The FEBS Journal, 278(12), 2034- 2043. Glycopeptide Antibiotics

Glycopeptide antibiotics are also known as dalbaheptides. Most of the glycopeptide

antibiotics were isolated from Actinomycetales.(30) As name suggests, glycopeptide antibiotics are decorated with carbohydrates. The function of carbohydrate is to deliver the antibiotic to its target site by enhancing its solubility.(30) Glycopetide antibiotics were introduced into clinical practices about fifty years ago.(31) The glycopeptide family consists of an aglycon portion of

fused macrocyclic ring and carbohyrates.(32)

Vancomycin and teicoplanin are two major drugs belonging to the class of glycopeptide

antibiotics.(33) Teicoplanin, which was discovered in Europe in the mid-1980’s, is currently in

phase IV clinical trials for the prevention of surgical site infections after total hip and knee

arthoplasty.(30,31) Vancomycin is currently in phase III clinical trials for the prevention of early

viridans Streptococcal sepsis after hematopoietic cell transplantation.(32) Vancomycin and

teicoplanin provide defense against a variety of infections caused by Enterococci, methicillin-

resistant Staphylococcus aureus (MRSA), and Clostidium difficile.(34)

Resistance to vancomycin was first observed in Enterococci in mid-1980’s.(35) Therefore,

telavacin and , semi-synthetic drugs, were developed to overcome the rise in microbial resistant strains.(32) Avoparcin, ristocetin and telavancin are other drugs that belong to

the class of glycopeptide antibiotics.(32)

30 Nicolaou, K. C., Boddy, C. N. C., Brase, S., Winssinger, N. 1999. Chemistry, Biology, & Medicine of the Glycopeptide Antibiotics. Angewandte Chemie International Edition, 38, 2096-2152. 31 Bambeke, F.V., Laethem, Y. V., Courvalin, P., Tulkens, P.M.2004. Glycopeptide Antibiotics from Conventional Molecules to New Derivatives. Drugs, 64, 913-936. 32 Jeya, M., Moon, H., Lee, K., Kim, I., Lee, J. 2011. Glycopeptide Antibiotics and their Novel Semi-Synthetic Derivatives. Current Pharmaceutical Biotechnology, 12, 1194-1204. 33 James, R. C., Pierce, J. G., Okano, A., Xie, J., Boger, D. L. 2012. Redesign of Glycopeptide Antibiotics: Back to the Future. American Chemical Society Chemical Biology., 7, 797-804. 34 Marshall, C. G., Lessard, I. A. D.; Park, I.S., Wright, G. D. 1998. Resistance Genes in Glycopeptide- Producing Organisms. Antimicrobial agents and chemotherapy, 42, 2215-2220. 35 Moellering, R. C. Jr. 1998. Vancomycin-Resistant Enterococci. Clinical Infectious Diseases, 26, 1196-1199. Sulfonamides

The general formula for is RSO2NH2. The first effective drugs were the

sulfonamides antibiotics.(36) Sulfonamide, trade named , was discovered in 1932 by

Gerhard Domagk.(37) It is the first drug to ever be discovered and used for a range of bacterial infections inside the body.

Sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase, which is an enzyme involved in folate synthesis. They are bacteriostatic and inhibit growth and multiplication of bacteria. Since many sulfonamides are rapidly excreted and very water soluble, they are mostly used to treat urinary tract infections. Sulfonamides also have some side effects.(38) For example, when used in large doses for the treatment urinary tract infection, porphyria, and hypersensitive reactions can occur; the drug has shown to cause strong allergic reactions. Some of the common trade names are sulfatrim, septra and co-trimoxazole. In 1942 the first clinical observation of sulfonamides for the treatment of diabetes was recorded. (39)

36 Sneader, W. 2001. History of Sulfonamides. eLS. 37 Otten, H. 1986. Domagk and the development of the sulphonamides. Journal of Antimicrobial Chemotherapy, 17(6), 689–696. 38 Knowles, S., Shapiro, L., Shear, N. H. 2001. Should Celecoxib Be Contraindicated in Patients Who Are Allergic to Sulfonamides? Drug Safety, 24 (4), 239–247. 39 Loubatières, A. 1957. The hypoglycemic sulfonamides: history and development of the problem from 1942 to 1955. Annals of the New York Academy of Sciences, 71, 4–11. Lipoglycopeptides

Lipoglycopeptides are a family of antibiotics that include , oritavancin, and

telvancin used primarily in treating various skin infections. Telavancin, trade name vibativ, was

approved in 2009 to be administered as a daily injection.(40) It was used in treating various skin

infections as well as treating gram-positive pneumonia.(41) Telavancin works by preventing the

synthesis of peptidoglycan, and by depolarizing the cell membrane, resulting in increased

membrane permeability.(42)

Dalbavancin, trade name Zeven, was discovered in 2005.(43) Like Telavancin,

Dalbavancin works to treat gram-positive pathogens, which is administered once a week.

Dalbavancin forms a complex with C-terminal d-ala-nyl-d-alanine of peptidoglycan chains,

resulting in the inhibition of bacterial cell wall biosynthesis.(43)

Oritavancin, trade name Nuvocid, was discovered in 2001 and is also administered as a once daily injection. Oritavancin has shown exceptional results in vitro activity against VRE,

MRSA, and gram-positive bacteria.(44) Of the three antibiotics, Telavancin is the only drug currently approved by the FDA for clinical use.(45) Dalbavancin and Oritavancin were both

declined by the FDA for clinical usage.

40 Smith, W. J., Drew, R. H. 2009. Telavancin: a new for gram-positive infections. Drugs Today, 45(3), 159- 173. 41 Plotkin, P., Patel, K., Uminski, A., Marzella, N. 2011. Telavancin (Vibativ), a New Option for the Treatment of Gram-Positive Infections. Pharmacy and Therapeutics Journal. 36(3), 127-138. 42 Damodaran, S. E., Madhan, S. 2011. Telavancin: A novel lipoglycopeptide antibiotic. Journal of Pharmacology and Pharmacotherapeutics, 2(2), 135-137. 43 Chen, A. Y., Zervos, M. J., Vazquez, J. A. 2007. Dalbavancin: a novel antimicrobial. International Journal of Clinical Practice, 61(5), 853-863. 44 Karaoui, L. R., El-Lababidi, R., Chahine, E. B. 20132013. Oritavancin: An investigational lipoglycopeptide antibiotic. American journal of health-system pharmacy, 70(1), 23-33. 45 Saravolatz, L. D., Stein, G. E., Johnson, L. B. 2009. Telavancin: A Novel Lipoglycopeptide. Clinical Infectious Diseases, 49(12), 1908-1914. First Generation Cephalosporins

Giuseppe Brotzu derived the first generation cephalosporins from a fungus,

Cephalosporium acremonium, in the year 1948. He observed that this fungus, Cephalosporium

acremonium, had the ability to inhibit the growth of multiple bacteria including, Staphylococcus

aureus and other gram-negative bacteria.(46)

This original antibiotic was modified by removing its natural side chain and by adding

unnatural side chains that increased its potency against microorganisms. There are 2 functional

groups at C-3 and C-7 that can be modified so that the antibiotic is more efficient in combatting

bacterial infections. A β-lactam ring is attached to a six-membered dihydrothiazine ring characterizes typical cephalosporins, because of the dihydrothiazine ring structure; they are resistant to β-lactamases. The dihydrothiazine ring has also been administered to patients as a substitute to penicillin, due of an allergy.(47)

Due to their diversity, this group of antibiotics has been separated into five different

generations. The mechanism of action utilized by cephalosporins is the inhibition of cell wall

development in gram-positive and gram-negative bacteria. It primarily attacks peptidoglycan, a

very unique polymer, that is vital to the cell wall of bacteria.(48) First generation cephalosporins,

Cefazolin and cephalexin, have been proven to be effective in inhibiting the growth of gram-

negative bacteria. It was first marketed in 1964; by Eli Lilly.(49) First generation cephalosporins

are still in use today and are commonly used to fight MSSA and spp..

46 Caprile, K. 1988. The cephalosporin antimicrobial agents: a comprehensive review. Journal of Veterinary Pharmacology and Therapeutics, 11(1), 1-32 47 Finberg R. W., Guharoy, R. 2012. Clinical Use of Anti-infective Agents: A Guide on How to Prescribe Drugs Used to Treat Infections, pg 31. 48 Scholar, E. M., vPratt, W. B. 2005. The Antimicrobial Drugs, second edition, pg 108. 49 Skatrud, P., Tietz, A. J., Ingolia, T. D., Cantwell, C. A., Fisher, D. L., Chapman, J. L., Queener, S. W. 1989. Use of recombinant DNA to improve production of cephalosporin by Cephalosporium acrenonium, Nature Biotechnology, 7(5), 477- 485.

Cephalosporin Third Generation

Cephalosporins are a class of β-lactam antibiotics drugs used to treat infections. It is derived from the fungus Acremonium. It is found in gram positive and gram negative bacteria.(50)

Cephalosporins were first isolated from Cephalosporium acremonium columns by Giuseppe

Brotzu in 1948. Gram negative bacteria cause the life threatening infections.(51) The desperate need for a of β-lactam drug occurred after resistance to penicillin occurred.(52) It was first

introduced in the late 1960’s and the first drug to be created was in 1976. The cephalosporin

drugs are available in 5 different generations. The third generation cephalosporins currently have

46 drugs on the market, 19 of which are generic. Its main purpose of the drugs is to treat and

prevent any bacterial infections that might occur such as soft tissue infections, and respiratory

tract infection. The most common third line drugs are Omnicef, Cefdiel, and Cedax, which are

all still available on the market but are not over the counter medicines.

50 Seeberg, A. H., Tolxdorff-Neutzling, R. M., Wiedemann, B. 1983. Chromosomal beta-lactamases of cloacae are responsible for resistance to third-generation cephalosporins. Antimicrobial agents and chemotherapy, 23(6), 918-925. 51 Kliebe, C., Nies, B. A., Meyer, J. F., Tolxdorff-Neutzling, R. M., Wiedemann, B. 1985. Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrobial Agents and Chemotherapy, 28(2), 302-307. 52 McDougal, L. K., Thornsberry, C. 1986. The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins. Journal of Clinical Microbiology, 23(5), 832-839. Fourth-Generation Cephalosporins

Fourth-generation cephalosporins, like second and third-generation cephalosporins, are

semi-synthetic antibiotics. These cephalosporins are synthesized from cephalosporin C, which is

produced by the fungus Cephalosporium acremonium. Cefepime, one of the first fourth-

generation cephalosporins, approved for clinical use along with cefpirome, which was

synthesized in the late 1980’s.(53) The experiments conducted on cefepime and cefpirome display

an enhanced effect on a broader spectrum of gram-negative and gram-positive microbes than the

earlier cephalosporins.(53,54,55,56)

This discovery led to the notion of a new generation of cephalosporins. These cephalosporins are easily distinguished by the presence of a quaternary ammonium group attached to the third carbon of the six-membered ring, known as group.(55) This

substituent provides a positive charge, which allows the molecule to become a zwitterion in

certain environments.(55,56,57) This feature contributes to the permeability of this class of cephalosporins. Early and current uses of these cephalosporins include treatment of gonorrhea, pneumonia, urinary tract infections, and skin infections.(57) Common names for cefepime and

cefpirome are maxipime and cefrom respectively. Other antibiotics in this class are currently

being tested.

53 Jauregui, I., Black, C. 1995. Clinical efficacy of cefepime in the therapy of bacterial infections. Drugs Today, 31, 241-247. 54 Pechere, J. 1995. Antibacterial activity of cefepime. Drugs Today, 31, 227-233. 55 Sanders, C. 1995. Cefepime, the next generation: the reasons and rationale behind its development. Drugs Today, 31, 221-225. 56 Sanders, C. 1993. Cefepime: the next generation? Clinical Infectious Diseases, 17(3), 369-379. 57 Garau, J., Wilson, W., Wood, M., Carlet, J. 1997. Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, and clinical utility. Clinical Microbiology and Infection, 3(1), S87-S101. Fifth Generation Cephalosporin’s The Fifth Generation cephalosporins are structurally and pharmacologically similar to the

penicillin’s. The Fifth Generation cephalosporins are synthetic drugs, specifically developed to

target resistant strains of bacteria and so far have proven to be effective against MRSA

(methicillin-resistant Staphylococcus aureus).(58) They have a β-lactam ring structure that

interferes with the synthesis of bacterial cell wall. Currently, ceftobiprole and ceftaroline are

classified as fifth generation cephalosporin. Ceftobiprole is capable of binding to penicillin’s

binding protein PBP2a, the protein that facilitates Staphylococcus aureus resistance to beta-

lactam antibiotics.(59) Ceftaroline was also structurally engineered to bind PBP2a, but is used to

treat different diseases and infections. Since its approval by the FDA in 2010, ceftaroline has

become popular for is ability to treat complicated skin and soft tissue infections, as well as,

4 community acquired pneumonia (Cap).(60, ) The fifth generation cephalosporins are not universally accepted and remain quite variable between countries. Ceftobiprole is currently only

available in Canada and is currently undergoing Phase III clinical trials in the U.S.

4. Chahine, E. B., Nornoo, A. O. 2007. Ceftobiprole: The First Broad-Spectrum Anti– methicillin-resistant Staphylococcus aureus Beta-Lactam". Journal of Experimental & Clinical MediTalbot GH, Thye D, Das A, Ge Y. Phase 2 study of ceftaroline versus standard therapy in the treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother 2007; 51:3612-6.cine 3 (1): 9–16, 2011. Reference does not make sense.

58 Kollef, M. H. 2009. New antimicrobial agents for methicillin-resistant Staphylococcus aureus. Critical care and resuscitation : Journal of the Australasian Academy of Critical Care Medicine, 11(4), 282–6. 59 Widmer, A. F. 2008. Ceftobiprole: a new option for treatment of skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus. Clinical Infectious Diseases, 46(5), 656–658. 60 Kaushik, D., Sudeep, R., Ankit, J. 2011. Ceftaroline: a comprehensive update. International Journal of Antimicrobial Agents, 37(5), 389–395.

Tetracyclines are a group of antibiotics generally used to inhibit bacterial growth. They are

used in the treatment of infections of the urinary tract, the intestines, treatment of chlamydia,

especially in patients allergic to β-lactams and macrolides.(61) They have also been used in the

prophylaxis, therapy of human and animal infections and also at sub-therapeutic levels in animal

feed as growth promoters. The first member of the group discovered was

(Aureomycin) in the late 1940s by Dr. Benjamin Duggar.(61) were derived from a

golden-colored, fungus-like, soil-dwelling bacterium named Streptomyces aureofaciens.(62)

Tetracycline penetrates bacterial cell wall by passive diffusion and inhibit the growth of

bacterial cell wall by destroying the membrane or protein synthesis.(62) New tetracycline

derivatives are being examined, although their role in treatment is not clear.(63) Trade names for

tetracyclines are Diabecline, Acnecycline, Tetra-abc, and Dyabetex.(63) Tetracycline molecules

comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached.

61 Chopra, I., Marilyn, R. 2001. Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance. Microbiology and molecular biology reviews, 65(2), 232-280 62 Levy, S. B., Mcmurry, L. M., Burdett, V., Courvalin, P., Hillen, W., Roberts, M. C., Taylor, D. E. 1989. Nomenclature for Tetracycline Resistance Determinants. Antimicrobial Agent and Chemotherapy, 33(8), 1373-1374. 63 Bochner, B. R., Huang, H-C., Schieven, G. L., Ames, B. M. 1980. Positive Selection for Loss of Tetracycline Resistance. Journal of Bacteriology, 143(2), 926-933. Antibiotic name: Diseases treated: m log P= Amikacin , -5.968

SMILESi : IUPAC: MIC values:

O=C(N[C@H]3[C@H](O[C@H]1O[C@@H] (2S)-4-Amino-N-[(2S,3S,4R,5S)-5-amino- Amikacin, was evaluated in vitro against

([C@@H](O)[C@H](N)[C@H]1O)CO)[C@ 2-[(2S,3R,4S,5S,6R)-4-amino-3,5- 219 clinical bacterial isolates. 181 of the dihydroxy-6-(hydroxymethyl)oxan-2- @H](O)[C@H](O[C@H]2O[C@H](CN)[C@ 219 strains had agar dilution minimal yl]oxy-4-[(2R,3R,4S,5R,6R)-6- @H](O)[C@H](O)[C@H]2O)[C@@H](N)C3 (aminomethyl)-3,4,5-trihydroxy-oxan-2- inhibitory concentration values of 8.0

)[C@@H](O)CCN yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxy- μg/ml or less for amikacin. butanamide:

Emp. Formula, Molar mass: Antibiotic group: Trade names: C22H43N5O13, 585.603g/mol Antibiotics Amikin, Briclin

Dipole Moment (Debye)= Molecular Volume= Surface Area= 6.28 Debye 531.67 Å3 561.49 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 277.816 Å2 37517-28-5 0.0118 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N): atoms): 17 18

References and summary a. MOA: The mechanism of action of amikacin is to introduce the aminohydroxyl butyryl chain into the streptamine section in kanamycin structure, which has higher in vitro anti-TB activity than kanamycin.( Zhang, Xia, and Jing Guo. "Advances in the treatment of pulmonary tuberculosis." Journal of thoracic disease 4.6 (2012): 617.)

b. Source: Amakacin is a semisynthetic derivative of . (Price, K. E., et al. "Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics." Antimicrobial agents and chemotherapy 5.2 (1974): 143-152.)

c. Cell line Test (MIC): amikacin, was evaluated in vitro against 219 clinical bacterial isolates. 181 of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 μg/ml or less for amikacin.( Kelly, Michael T., and John M. Matsen. "In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics." Antimicrobial agents and chemotherapy 9.3 (1976): 440-447.)

d. Human clinical trials: Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model. (Du, Ming, et al. "Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model." Journal of molecular medicine 84.7 (2006): 573-582.)

e. Review Article: Price, K. E., et al. "Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics." Antimicrobial agents and chemotherapy 5.2 (1974): 143-152. Zhang, Xia, and Jing Guo. "Advances in the treatment of pulmonary tuberculosis." Journal of thoracic disease 4.6 (2012): 617 Kelly, Michael T., and John M. Matsen. "In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics." Antimicrobial agents and chemotherapy 9.3 (1976): 440-447. f. Du, Ming, et al. "Clinical doses of amikacin provide more effective suppression of the human CFTR-G542X stop mutation than gentamicin in a transgenic CF mouse model." Journal of molecular medicine 84.7 (2006): 573-582.

Antibiotic name Amioxicillin Diseases treated Bacterial m log P -1.352 Infection

• SMILES IUPAC (2S,5R,6R)-6-{[(2R)-2- MIC values 99.99% was obtained for O=C(O)[C@@H]2N3C(=O)[C@@H amino- 2-(4-hydroxyphenyl)- strains with an MIC of 4 mg/L, ≥99% for

](NC(=O)[C@@H](c1ccc(O)cc1)N) acetyl]amino}-3,3-dimethyl-7- strains with an MIC of 8 mg/L and 70.6%

[C@H]3SC2(C)CCC3(C)S[C@@H]2 oxo-4-thia-1- for the strain with an MIC of 16 mg/L at

[C@H](NC(=O)[C@H](N)c1ccc(O)c azabicyclo[3.2.0]heptane-2- 24 h sampling time against

c1)C(=O)N2[C@H]3C(O)=O carboxylic acid

Emp. Formula, Molar mass C H N O S Antibiotic group Peniclillins Trade names Amoxil, Polymox, Trimox, 16 19 3 5 365.4 g/mol Wymox

Dipole Moment (Debye)3.96 Debye Molecular Volume 339.70 Å3 Surface Area 367.32 Å2

Surface Area (TPSA) 132.957 Å2 CAS Number 26787-78-0 D/V (dipoe moment/volume) 0.0116 Debye/ Å3

Rotatable # bonds 4 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 5 atoms) 8

References and summary a. MOA This drug acts by inhibiting the synthesis of bacterial cell walls. (Fisher, J. F.; Meroueh, S. O.; Mobashery, S. 2005. "Bacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity†". Chemical Reviews 105 : 395–424.

b. Source Amoxicillin is a moderate-spectrum, bacteriolytic, β-lactam antibiotic in the . (Raviña, E (2011). The Evolution of Drug Discovery. Weinheim: Wiley-VCH. p. 262)

c. Cell line Test The purpose of the study was to examine the effects of veterinary antibiotics such as amoxicillin (AMX) on the biochemical mechanism of human embryonic cells (HEK293. Kim, H, Kim, K, & Kim, S 2012, 'Biochemical Effects of Veterinary Antibiotics on Proliferation and Cell Cycle Arrest of Human HEK293 Cells', Bulletin Of Environmental Contamination & Toxicology, 89:234-239) (MIC)

d. Human clinical This study was conducted in order to determine if patients positive for A. actinomycetemcomitans with moderate to advanced periodontitis benefit specifically from amoxicillin plus metronidazole given as an adjunct to full-mouth scaling and root planning. As a result, patients who were positive for A. actinomycetemcomitans had no specific benefit from amoxicillin plus metronidazole. (Mombelli, A, Cionca, N, Almaghlouth, A, Decaillet, F, Courvoisier, D, & Giannopoulou, C n.d., 'Are There Specific Benefits of Amoxicillin Plus Metronidazole in Aggregatibacter actinomycetemcomitans-Associated Periodontitis? Double-Masked, Randomized Clinical Trial of Efficacy and Safety', Journal Of Periodontology, 84, 6, pp. 715-724) trials e. Review Article This review is to assess the evidence regarding efficacy of oral amoxicillin compared to standard treatment for WHO-defined severe community acquired pneumonia in under-five children in developing country. (Das, R, & Singh, M 2013, 'Treatment of Severe Community-Acquired Pneumonia with Oral Amoxicillin in Under- Five Children in Developing Country: A Systematic Review', Plos ONE, 8, 6, pp. 1-10)

Antibiotic name Diseases treated m log P Ampicillin Urinary tract infection, Gonorrhea, Salmonella =-0.873 infections

SMILES IUPAC MIC values O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O (2S,5R,6R)-6-([(2R)-2-amino-2- 0.125-16 µg/ml, Streptococcus )[C@@H](c1ccccc1)N)[C@H]3SC2(C)C phenylacetyl]amino) pneumoniae -3,3-dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C16H19N3O4S, 349.41 g/mol Penicillin Omnipen, Polycillin, Principen

Dipole Moment (Debye) Molecular Volume Surface Area 3.64 Debye 333.04 Å3 356.26 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 112.729 Å2 69-53-4 0.012 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 7

References and summary a. MOA It inhibits the final stage of bacterial cell wall synthesis in binary fission, which leads to cell . (Matsuhashi, S., et al, Mechanism of Action and Development of Resistance to a New Amidino Penicillin, J. Bacteriol, 117(2) p. 578- 587, 1974)

b. Source The natural source for the class of Penicillin antibiotics was originally derived from the fungus, Penicillium chrysogenum. (Albang, R., et al, Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum, Nat. Biotech., 26 p. 1161-1168, 2008)

c. Cell line Test (MIC) 0.125-16 µg/ml, Streptococcus pneumonia (Lacy, M., et al, Pharmacodynamic Comparisons of Levofloxacin, Ciprofloxacin, and Ampicillin against Streptococcus pneumoniae in an In Vitro Model of Infection, Antimicrob. Agents Chemother., 43(3) p. 672-677, 1999)

d. Human clinical trials Linezolid is active against these foot infection pathogens. The results were compared to oral formulations with that of intravenous ampicillin-. (Lipsky, B., et al, Treating Foot Infections in Diabetic Patients: A Randomized, Multicenter, Open-Label Trial of Linezolid versus Ampicillin-Sulbactam/Amoxicillin-Clavulanate, Clin. Infect. Dis., 38(1) p. 17-24, 2004)

e. Review Article A blind study was conducted concerning the effect of lactic acid producing bacteria on the intestinal microflora during ampicillin treatment. (Black, F., et al, Effect of lactic acid producing bacteria on the human intestinal microflora during ampicillin treatment, Scan. J. Infec. Dis., 23(2) p.247-254, 1991)

Antibiotic name Diseases treated m log P Arsphenamine Syphillis = 0.566

SMILES IUPAC MIC values C1=CC(=C(C=C1[As]=[As]C2=CC(=C(C=C2) 2-amino-4-(3-amino-4- (None found) O)N)N)O hydroxyphenyl)arsanylidenears anylphenoll

Emp. Formula, Molar mass Antibiotic group Trade names C12H12As2N2O2 , 366.07908 g/mol Arsenical Compound Salvarsan

Dipole Moment (Debye) Molecular Volume Surface Area 1.01 Debye 263.69 A3 87.422 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 92.502 A2 139-93-5 0.0038 Debye/ A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 4 4

References and summary a. MOAThe mechanism of action for arsphenamine is that it is bacteriostatic to bacteria. (Lansdown, A. B. G. "Silver I: its antibacterial properties and mechanism of action." Journal of wound care 11.4 (2002): 125-131.)

b. SourceArsphenamine is an organoarsenic molecule.( Pergantis, Spiros A., Witold Winnik, and Don Betowski. "Determination of Ten Organoarsenic Compounds Using MicroboreHigh-performance Liquid Chromatography Coupled With Electrospray MassSpectrometry–Mass Spectrometry." J. Anal. At. Spectrom. 12.5 (1997): 531-536.)

c. Cell line Test (MIC)No recent MIC values. This drug was used in the 1910’s. (Discontinued in 1940’s)

d. Human clinical trialsArsphenamine was tested against syphilis. (Modell, Walter, and Doris J. Place. "Treatment of Infections." The Use of Drugs. Springer Berlin Heidelberg, 1957. 60-86.)

e. Review Article(Modell, Walter, and Doris J. Place. "Treatment of Infections." The Use of Drugs. Springer Berlin Heidelberg, 1957. 60-86.) f. (Stokes, John H., and Herman Beerman. "The trivalent arsenicals in syphilis: Some recent advances, comparisons and evaluations." The American Journal of the Medical Sciences 201.4 (1941): 611-625.)

Antibiotic name: Diseases treated: m log P= Azithromycin Ear infection, Strep throat 2.725

SMILES: IUPAC : MIC values: CN(C)[C@H]3C[C@@H](C)O[C@@H](O[C (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)- MIC value is 0.5 mg/l for azithromycin @@H]2[C@@H](C)[C@H](O[C@H]1C[C@ 2-ethyl-3,4,10-trihydroxy- against Coagulase-negative 3,5,6,8,10,12,14-heptamethyl-15-oxo- @](C)(OC)[C@@H](O)[C@H](C)O1)[C@@ 11-{[3,4,6-trideoxy-3-(dimethylamino)- staphylococci H](C)C(=O)O[C@H](CC)[C@@](C)(O)[C@ β-D-xylo-hexopyranosyl]oxy}-1-oxa-6- H](O)[C@@H](C)N(C)C[C@H](C)C[C@@]2 azacyclopentadec-13-yl 2,6-dideoxy-3- (C)O)[C@@H]3O C-methyl-3-O-methyl-α-L-ribo- hexopyranoside

Emp. Formula, Molar mass: Antibiotic group: Trade names: C38H72N2O12, 748.996g/mol Azyth, Zithromax, Azithrocin, Azin, Zeto

:

Dipole Moment (Debye)= Molecular Volume= Surface Area: 3.05 Debye 736.447 Å3 760.40 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 180.091 Å2 83905-01-5 0.00414 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N): atoms): 5 13

References and summary a. MOA: the mechanism of action of azithromycin is that they prevent the bacteria from growing by interfering with their protein synthesis and they do this by binding to the 50S subunit of the bacterial ribosomes which inhibits the translation of mRNA. (azithromycin (Zithromax, Zmax, Z-Pak) - Side Effects, Drug Interactions". MedicineNet. Retrieved 2013-01-06)

b. Source: The main source for azithromycin is erythromycin. (ERYTHROMYCIN, IN. "Actinomycete Antibiotics." The Journal of biological chemistry 237.2 (1962).)

c. Cell line Test (MIC): A cell line test was carried out to investigate the activity concentration of azithromycin against intracellular growth of two clinical isolates of legionell pneumophila. The MIC value of azithromycin was 0.5 mg/l of the intracellular acting antibiotic. (Jonas, Daniel, et al. "The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo." Journal of Antimicrobial Chemotherapy 46.3 (2000): 385-390.) d. Human clinical trials: Human clinical trials have been carried out with azithromycin. One of the clinical trial was the pharmacokinetic of azithromycin in human serum and tissue. (Foulds, G., R. M. Shepard, and R. B. Johnson. "The pharmacokinetics of azithromycin in human serum and tissues." Journal of Antimicrobial Chemotherapy 25.suppl A (1990): 73-82.)

e. Review Article: azithromycin (Zithromax, Zmax, Z-Pak) - Side Effects, Drug Interactions". MedicineNet. Retrieved 2013-01-06. ERYTHROMYCIN, IN. "Actinomycete Antibiotics." The Journal of biological chemistry 237.2 (1962). Jonas, Daniel, et al. "The effect of azithromycin on intracellular Legionella pneumophila in the Mono Mac 6 cell line at serum concentrations attainable in vivo." Journal of Antimicrobial Chemotherapy 46.3 (2000): 385-390. Foulds, G., R. M. Shepard, and R. B. Johnson. "The pharmacokinetics of azithromycin in human serum and tissues." Journal of Antimicrobial Chemotherapy 25.suppl A (1990): 73-82. f.

Antibiotic name Diseases treated m log P Pseudomonas Infection =0.991

SMILES IUPAC MIC values O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O (2S,5R,6R)-3,3-dimethyl-7-oxo-6- 25 μg/mL when tested for Enterobacter, )[C@@H](c1ccccc1)NC(=O)N2C(=O)NCC2) {[(2R)-2-{[(2-oxoimidazolidin-1- [C@H]4SC3(C)C yl)carbonyl]amino}-2- phenylacetyl]amino}-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C20H23N5O6S acylampicillin Azlin, Securopen

Dipole Moment (Debye) Molecular Volume Surface Area 8.42 Debye 427.21 Å3 119.93 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 148.14 Å2 37091-66-0 0.070 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 4 11

References and summary a. MOA Azlocillin binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall (Baker, C., et al. In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against and , including beta-lactamase-producing strains, Antimicrobial agents and chemotherapy ,(17)4, p.757-761, 1980.) l

b. Source Azlocillin is a semisynthetic drug (Fu, K., et al. Azlocillin and mezlocillin: new ureido penicillins. Antimicrobial agents and chemotherapy, (13)6,p. 930-938, 1978)

c. Cell line Test (MIC) An MIC value of 25 μg/mL when tested for Enterobacter . (Fu, K., et al. Azlocillin and mezlocillin: new ureido penicillins. Antimicrobial agents and chemotherapy, (13)6,p. 930-938, 1978)

d. Human clinical trials This study was carried out on Azlocillins to test its efficacy in treatment of Neisseria gonorrhoeae and Haemophilus (Baker, C., et al. In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains, Antimicrobial agents and chemotherapy ,(17)4, p.757-761, 1980.). e. Review Article A review on the efficacy of Azlocillin in treatment of Pseudomonas aeruginosa community-acquired pneumonia was carried out. (Hatchette, et al. Pseudomonas aeruginosa community-acquired pneumonia in previously healthy adults: case report and review of the literature. Clinical infectious diseases (31)6, p.1349-1356, 2000.)

Antibiotic name Diseases treated m log P Aztreonam Urinary Tract Infections = -3.672

SMILES IUPAC MIC values O=S(=O)(O)N2C(=O)[C@@H](NC(=O)C 2-({[(1Z)-1-(2-amino-1,3- 0.25 μg/ml used on Klebsiella (=N\OC(C(=O)O)(C)C)/c1nc(sc1)N)[C@ thiazol-4-yl) -2- {[(2S,3S)-2- pneumoniae @H]2C methyl-4-oxo-1-sulfoazetidin- 3-yl]amino} -2- oxoethylidene]amino}oxy)-2- methylpropanoic acid Emp. Formula, Molar mass Antibiotic group Trade names C13H17N5O8S2, 435.438 g/mol Azactam

Dipole Moment (Debye) Molecular Volume Surface Area 3 2 6.12 Debye 365.26 Å 419.38 Å

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 181.512 Å2 78110-38-0 0.0168 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 5 13

References and summary a. MOA Monobactam’s mechanism of action is the inhibition of the peptidoglycan synthesis that is present in bacterial cell walls. (Kohanski, M., Dwyer, D., and Collins, J., How Antibiotics Kill Bacteria: From Targets to Networks, Nature Reviews Microbiology, Vol. 8, p. 423-435, 2010)

b. Source are produced by Acetobacter spp. and Abrobacterium radiobacter. (O’Sullivan, J., et al., Biosynthesis of monobactam compounds: origin of the carbon atoms in the beta-lactam ring, Antimicrobial Agents and Chemotherapy, Vol. 21, No. 4, p. 558-564, 1982)

c. Cell line Test (MIC) Aztreonam was used on K. pneumonia to determine its MIC value. (Babini, G., and Livermore, D., Are SHV β-Lactamases Universal in ?, Antimicrobial Agents and Chemotherapy, Vol. 44, No. 8, p. 2230, 2000)

d. Human clinical trials Aztreonam was clinically tested to determine its safety on 364 patients. (Newman, T., Dreslinski, G., and Tadros, S., Safety Profile of Aztreonam in Clinical Trials, Clinical Infectious Diseases, Vol. 7, Issue 4, p. 648-655, 1985)

e. Review Article Review article about the use of Aztreonam on paediatric bone and joint infections. (Scott, N., Review article: paediatric bone and joiont infection, Journal of Orthopaedic Surgery, Vol. 9, No. 1, p. 83-90, 2001)

Antibiotic name Diseases treated m log P Bacampicillin Tonsillitis, Pneumonia, =1.76

SMILES IUPAC MIC values

[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@ 1-Ethoxycarbonyloxyethyl 12µg/mL when tested for inhibition

H]2NC(=O)[C@H](N)C1=CC=CC=C1)C(=O) (2S,5R)-6-[[(2R)-2-amino-2- against chronic bronchitis with purulent

OC(C)OC(=O)OCC phenylacetyl]amino]-3,3- sputum.

dimethyl-7-oxo-4-thia-1-

azabicyclo[3.2.0]heptane-2-

carboxylate

Emp. Formula, Molar mass Antibiotic group Trade namesSpectrobid

C21H27N3O7S , 465.519 g/mol Penicillins

Dipole Moment (Debye) Molecular Volume Surface Area 5.13 Debye 459.00 Åᶾ 109.116 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 137.274 Ų 50972-17-3 0.0112 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA Bacampicillin inhibits cell wall mucopeptides, while absorbing the GI tract. (Magni, L., et al. "Clinical pharmacological studies with bacampicillin." Penicillins and Cephalosporins. Springer US, 1976. 109-114.

b. Source Bacampicillin came from Ampicillin. (Bodin, N-O., et al. "Bacampicillin: a new orally well-absorbed derivative of ampicillin." Antimicrobial agents and chemotherapy 8.5 (1975): 518-525.

c. Cell line Test (MIC) A cell line test of 12µg/mL was carried out to test for inhibition against chronic bronchitis with purulent sputum. (Davies, B., and F. Maesen. "Serum and sputum antibiotic levels after ampicillin, amoxycillin and bacampicillin in chronic bronchitis patients." Infection 7.5 (1979): S465-S468.

d. Human clinical trials A human clinical trial was carried out to test for in vitro lymphocyte response to Bacampicillin in allergic patirnts. (Cederbrant, Karin, M. Marcusson‐StÅhl, and Per Hultman. "Characterization of primary recall in vitro lymphocyte responses to bacampicillin in allergic subjects." Clinical & Experimental Allergy 30.10 (2000): 1450-1459.

e. Review Article Bacampicillin along with Thiamine is transported in Caco-2 cell. (Oda, Masako, et al. "Bacampicillin uptake is shared with thiamine in caco-2 cells." Biological and Pharmaceutical Bulletin 30.7 (2007): 1344.

Bacampicillin along with amoxicillin and ampicillin was produced for gram-negative antimicrobial activity. (Wright, Alan J. "The penicillins." Mayo Clinic Proceedings. Vol. 74. No. 3. Elsevier, 1999.

Antibiotic name Diseases treated m log P Bacitracin Treats external eye infection =2.343

SMILES IUPAC MIC values CC[C@H](C)[C@H](N)C1=N[C@@H](CS1)C(= (4R)-4-[(2S)-2-{[(4R)-2-[(1S,2S)-1-amino-2- 0.0625-32µg/ mol for bacteria on O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)= methylbutyl]-4,5-dihydro-1,3-thiazol-4- yl]formamido}-4-methylpentanamido]-4- Mueller-Hinton agar plates O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@ H]1CCCCNC(=O)[C@H](CC(N)=O)NC(=O)[C@ {[(1S,2S)-1-{[(3S,6R,9S,12R,15S,18R,21S)- @H](CC(O)=O)NC(=O)[C@H](CC2=CNC=N2)N 18-(3-aminopropyl)-12-benzyl-15-[(2S)- C(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@ butan-2-yl]-3-(carbamoylmethyl)-6- @H](NC(=O)[C@@H](CCCN)NC1=O)[C@@H (carboxymethyl)-9-(1H-imidazol-4- ](C)CC ylmethyl)-2,5,8,11,14,17,20-heptaoxo- 1,4,7,10,13,16,19- Emp. Formula, Molar mass Antibiotic group Trade names C66H103N17O16S Polypeptide Baciim 1422.69 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 14.82 Debye 1428.59 Å3 418.661 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 530.863 Å2 1405-87-4 0.01037 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 31 available, attached to O, S, N) atoms) 20 33

References and summary a. MOA The mechanism of action for this drug is it interferes with the dephosphorylation of isopropyl pyrophosphate. (Stone, K. John, and Jack L. Strominger. "Mechanism of action of bacitracin: complexation with metal ion and C55-isoprenyl pyrophosphate." Proceedings of the National Academy of Sciences 68.12 (1971): 3223-3227.)

b. Source The natural source of bacitracin is from a strain called Bacillus licheniformis. (Stone, K. John, and Jack L. Strominger. "Mechanism of action of bacitracin: complexation with metal ion and C55-isoprenyl pyrophosphate." Proceedings of the National Academy of Sciences 68.12 (1971): 3223-3227.)

c. Cell line Test (MIC) The MIC is between 0.0625-32µg/ mol when tested on bacteria on Mueller-Hinton agar plates. (McAnally, T. P., M. R. Lewis, and D. R. Brown. "Effect of rifampin and bacitracin on nasal carriers of Staphylococcus aureus." Antimicrobial agents and chemotherapy 25.4 (1984): 422-426.)

d. Human clinical trials Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex Disease in Patients With AIDS. The study was about finding a safeness, effectiveness, and toxicity of topical trifluridine in treating mucocutaneous (at the nasal, oral, vaginal, and anal openings) Herpes simplex virus (HSV) disease that has shown resistance to acyclovir in HIV-infected patients. The trial has completed Phase 4.

e. Review Article The Peptide Antibiotics of Bacillus: Chemistry, Biogenesis, and Possible Functions (Katz, Edward, and Arnold L. Demain. "The peptide antibiotics of Bacillus: chemistry, biogenesis, and possible functions." Bacteriological reviews 41.2 (1977): 449.) The article includes all the background information on the drug ranging from the chemistry aspect to the biology aspect of the drug.

Antibiotic name Diseases treated Urinary tract m log P = 0.162 Balofloxacin infections

SMILES IUPAC MIC values CNC1CCCN(C1)C2=C(C=C3C(=C2OC)N(C=C 1-Cyclopropyl-6-fluoro-8-methoxy- Pseudomonas aeruginosa: MIC50 - 6.25 (C3=O)C(=O)O)C4CC4)F 7-(3-methylaminopiperidin-1-yl)-4- µg/ml and MIC90 - 50 µg/ml oxoquinoline-3-carboxylic acid

Escherichia coli: MIC50 – 0.20 µg/ml and MIC90 – 1.56 µg/ml

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C20H24FN3O4 Third Generation Quinolone Baloxin, Balofox, Balorain Molar Mass: 389.427 g/mol Antibiotics

Dipole Moment (Debye) Molecular Volume Surface Area 7.68 Debye 382.55 Å3 392.36 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 83.803 Å2 127294-70-6 0.02 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 2 7

References and summary a. MOA Balofloxacin does activity going against gram-positive bacteria, thus inhibiting the synthesis of the cell wall. (Jain, PS., Redasani, VK., Patil, VK., Patil, MS., Gawad, JB., Reversed-Phase TLC/Densitometry Method for Estimatino of Balofloxacin In Bulk and In Tablet Dosage Form, J., Int., Adv., Res., 1(7), 257-262, 2013). 1

b. Source Infectious enteritis and Shigella spp. (Obana, M., Irimajiri, S., Tomizawa, I, Takizawa, Y., Sakamoto, Y., Nitta, Y., Tsunoda, T., Fukuda, H., Yamaguchi, T., Masuda, G., Clinical study of balofloxacin on infectious enteritis and assessment of the fecal drug concentration and intestinal microbial flora in patients with inpatients with infectious enteritis. Research group of balofloxacin on infectious enteritis, Ann., Intern., Med., 69(9), 991-1006, 1995). 4

c. Cell line Test (MIC) Pseudomonas aeruginosa: MIC50 - 6.25 µg/ml and MIC90 - 50 µg/ml Escherichia coli: MIC50 – 0.20 µg/ml and MIC90 – 1.56 µg/ml (Sawae, Y., Okada, K., Takaki, K., Misumim, H., Shimono, N., Kuboi, Satoshi., Eguchi, K., Niho, Y., Basic and clinical studies of balofloxacin in the field of internal medicine, Jpn. J. Chemother., 43 (5), 253-258, 1995). 2

d. Human clinical trials Phase 2 trials for Respiratory Tract Infection in 2002 Phase 3 trials for Urinary Tract Infections were completed in 2001. (Alksne, L., Balofloxacin Choongwae, Curr Opin Investig Drugs, 4(2), 224-229, 2003). 3

e. Review Article 1) Jain, PS., Redasani, VK., Patil, VK., Patil, MS., Gawad, JB., Reversed-Phase TLC/Densitometry Method for Estimatino of Balofloxacin In Bulk and In Tablet Dosage Form, J., Int., Adv., Res., 1(7), 257-262, 2013. 2) Sawae, Y., Okada, K., Takaki, K., Misumim, H., Shimono, N., Kuboi, Satoshi., Eguchi, K., Niho, Y., Basic and clinical studies of balofloxacin in the field of internal medicine, Jpn., J., Chemother., 43 (5), 253-258, 1995. 3) Alksne, L., Balofloxacin Choongwae, Curr Opin Investig Drugs, 4(2), 224-229, 2003. 4) Obana, M., Irimajiri, S., Tomizawa, I, Takizawa, Y., Sakamoto, Y., Nitta, Y., Tsunoda, T., Fukuda, H., Yamaguchi, T., Masuda, G., Clinical study of balofloxacin on infectious enteritis and assessment of the fecal drug concentration and intestinal microbial flora in patients with inpatients with infectious enteritis. Research group of balofloxacin on infectious enteritis, Ann., Intern., Med., 69(9), 991-1006, 1995.

Antibiotic name Diseases treated m log P 1.327 Carbenicillin Urinary Tract Infections

SMILES IUPAC MIC values CC1([C@@H](N2[C@H](S1)[C@@H](C2= (2S,5R,6R)-6- Pseudomonas, 50 μg/mL - 100 μg/mL O)NC(=O)C(C3=CC=CC=C3)C(=O)O)C(=O)O {[carboxy(phenyl)acetyl]amino}- )C 3,3-dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptanes -2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C17H18N2O6S, 378.401 g/mol Penicillins Geocillin

Dipole Moment (Debye) Molecular Volume Surface Area 6.82 Debye 348.87 Å3 374.89 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 124.005 Å2 4697-36-3 0.196 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 3 8

References and summary a. MOA Carbenicillin is bactericidal and works by interrupting cell wall synthesis and production of peptidoglycan. (Suginaka, Hidekazu, Akira Ichikawa, and Shozo Kotani. “Penicillin-Resistant Mechanisms in Pseudomonas aeruginosa: Effects of Penicillin G and Carbenicillin on Transpeptidase and D-Alanine Carboxypeptidase Activities.” Antimicrobial Agents and Chemotherapy, Vol. 6, No. 6, 672-675, 1974.)

b. Source Carbenicillin is a semi-synthetic antibiotic derived from penicillin. Many derivatives of Carbenicillin have been synthesized by adding different functional groups to its structure. (Clayton, J. Peter, Martin Cole, Stephen W. Elson, Kenneth D. Hardy, Linda W. Mizen. and Robert Sutherland. “Preparation, Hydrolysis, and Oral Absorption of a-Carboxy Esters of Carbenicillin. Journal of Medicinal Chemistry, Vol. 18, No. 9, 172-177, 1975.) ,

c. Cell line Test (MIC) Cell line tests were conducted to compare the efficacy of Carbenicillin, Gentamicn, and both drugs together. Results indicated Carbenicillin having MIC values from 50 μg/mL to 100 μg/mL and also showed a synergistic effect when both drugs were administered lowering MIC values significantly. (Sonne, Minetta and Ernest Jawetz. “Combined Action of Carbenicillin and Gentamicin on Pseudomonas aeruginosa In Vitro.” Applied Microbiology Vol. 17, No. 6, 893-896, 1969.) d. Human clinical trials Clinical Studies performed by Overturf et. al. found Carbenicillin to a viable treatment option for meningitis caused by certain bacterial strains, however they noted there were some more effective treatments available. (Overturf, G. D., E. A. Steinberg, A. E. Underman, J. Wilkins, J. M. Leedom, A. W. Mathies, JR., and P. F. Wehrle. “Comparative Trial of Carbenicillin and Ampicillin Therapy for Purulent Meningitis.” Antimicrobial Agents and Chemotherapy, Vol. 11, No. 3, 420-426, 1977.)

e. Review Article (Seginková, Z., V. Krčméry and H. Knothe “Ceftazidime Resistance in Pseudomonas aeruginosa: Transduction by a Wild-Type Phage.” The Journal of Infectious Diseases, Vol. 154, No. 6, 1049-1050, 1986.)

Antibiotic name Diseases treated m log P Cefacetrile Mammary infections in cows = -1.68

SMILES IUPAC MIC values

O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R)-3-(acetyloxymethyl)- 63 µg/mL when tested for antibiotics

=O)CC#N)COC(=O)C)C(=O)O 7-[(2-cyanoacetyl)amino]- 8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C13H13N3O6S, 339.325 g/moll First generation cephalosporin Celospor, Celtol, Cristacef antibiotic

Dipole Moment (Debye) Molecular Volume Surface Area 5.7 Debye 281.80Å3 294.15Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 136.803 Ų 10206-21-0 0.020 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA Cefacetrile inhibits cell wall synthesis. (Christ, W. "Pharmacological properties of cephalosporins." Infection 19 (1991): S244-S252.

b. Source Cefacetrile is a Cephalosporin antibiotic with a Beta-lactam ring. (Prescott, John F. "Beta-lactam antibiotics: cephalosporins." Antimicrobial Therapy in Veterinary Medicine (2006): 139-158.

c. Cell line Test (MIC) A cell line test of 63 µg/mL was carried out to test for antibiotics in ewe and goat milk. (Beltrán, M. C., et al. "Evaluation of the Charm maximum residue limit β-lactam and tetracycline test for the detection of antibiotics in ewe and goat milk." Journal of dairy science 96.5 (2013): 2737-2745.

d. Human clinical trials A clinical trial was carried out to determine the efficacy of Cefacetrile with treatment of bovine . (Tripathy, S. B., and A. B. Murty. "Treatment of bovine mastitis with cefacetrile." Indian Veterinary Journal 67.12 (1990): 1167-1168.

e. Review Article Chromatography was used to determine Cefacetrile in milk. (Grzelak, Edyta M., Irena Malinowska, and Irena M. Choma. "Determination of cefacetrile and cefuroxime residues in milk by thin-layer chromatography." Journal of Liquid Chromatography & Related Technologies® 32.14 (2009): 2043-2049.

Cefacetrile was tested on inflammed mammary glands in cows. (BURMAŃCZUK, ARTUR, et al. "Concentration of cefacetril in milk after its intramammary administration to cows with healthy and inflammed mammary gland." Bull Vet Inst Pulawy 55 (2011): 685-688.

Antibiotic name Diseases treated m log P Cefaclor Pnemonia and infections of ear = -1.699

SMILES IUPAC MIC values

O=C2N1/C(=C(/Cl)CS[C@@H]1[C@@H]2 (6R,7R)-7-{[(2R)-2-amino-2- 0.25µg/ml when testing for Neisseria

NC(=O)[C@@H](c3ccccc3)N)C(=O)O.O phenylacetyl]amino}- 3-chloro-8- gonorrhoeae

oxo-5-thia-1-

azabicyclo[4.2.0]oct-2-ene- 2-

carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C15H14ClN3O4S,367.808 g/mol Cephalosporins Ceclor

Dipole Moment (Debye) Molecular Volume Surface Area 7.36 Debye 367.813 Å3 91.42 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 112.729 Å2 53994-73-3 0.020 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 7

References and summary a. MOA Cefaclor inhibits cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall (Shigi, Y., et al.Mechanism of action of the new orally active cephalosporin. The Journal of antibiotics. (37)7, p.790-796, 1984).

b. Source Cefaclor is produced by synthetic processes (Appel, L., et al. Process for producing a tablet core aperture, 1993).

c. Cell line Test (MIC) An MIC value of0.25µg/ml was obtained when testing for Neisseria gonorrhoeae (Bill, N., et al. Comparison of in vitro activity of cephalexin, cephradine, and cefaclor. Antimicrobial agents and chemotherapy, (11)3, p. 470-474, 1977.)

d. Human clinical trials A human clinical trial was carried out to compare cefaclor and -sulfamethoxazole in treatment of acute otitis (Marchant, C., et al. A randomized controlled trial of cefaclor compared with trimethoprim-sulfamethoxazole for treatment of acute . The Journal of pediatrics,p.(105)4,p.633-638, 1984)

e. Review Article A review was carried out to test the efficacy of cefaclor in pharmacology and pharmacokinetics. (Sides, G., et al. A comprehensive review of the clinical pharmacology and pharmacokinetics of cefaclor. Clinical therapeutics p. 5-19, 1987.).

Antibiotic name Diseases treatedModerate m log P -1.965 Cefadroxil infections like “strep throat”

SMILESO=C2N1/C(=C(\CS[C@@H]1[C@@ IUPAC (6R,7R)-7-{[(2R)-2-amino- MIC values H]2NC(=O)[C@@H](c3ccc(O)cc3)N)C)C(= 2-(4-hydroxyphenyl)acetyl] 15 µg/mL; Staphylococci, Streptococci, O)O.O amino}-3-methyl-8-oxo-5-thia-1- M. Cartarrhalis, and H. Influenzae azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names -1 C16H17N3O5S, 363.389 gmol Cephalosporin (first generation) Duracef ®

Dipole Moment (Debye) Molecular Volume Surface Area 3.30 Debye 301.212 Å3 382.61 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 132.957 Å2 66592-87-8 0.012 Debye/ Å2

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 5 8

References and summary a. MOA Cefadroxil is a bactericidal, β-lactam antibiotic that works by breaking down cell walls of susceptible bacteria. (Jager , Simon A.W., Peter A. Jekel, Dick B. Janssen. Hybrid penicillin acylases with improved properties for synthesis of β -lactam antibiotics. Enzyme and Microbial Technology, 40, 1335–1344, 2007.)

b. Source Cefadroxil is a β-lactam antibiotic from the cephalosporin family. Like all Cephalosporin antibiotic, Cefadroxil is derived from penicillin acylase and altered with site directed mutagenesis. (Jager , Simon A.W., Peter A. Jekel, Dick B. Janssen. Hybrid penicillin acylases with improved properties for synthesis of β -lactam antibiotics. Enzyme and Microbial Technology, 40, 1335–1344, 2007.)

c. Cell line Test Staphylococci, Streptococci, M. Cartarrhalis, and H. Influenzae (MIC) 15 µg/mL (MacGowan, A.P., Richard wise. Establishing MIC breakpoints and the Interpretations on In-vitro Susceptibility Tests. Journal of Anitmicrobial Chemotherapy. 48, 17-28, 2001.)

d. Human clinical There have been three completed clinical trials and there is currently one underway that has reached phase 4. trials ClinicalTrials.gov indentifier(s): NCT00834275, NCT00835081, NCT01244698, NCT00405158.

e. Review Article Hernanto M, Yudani B, Pudjiati S, Indrastuti N. DRESS syndrome from cefadroxil confirmed by positive patch test. Allergy. 62(10), 1216-1217, 2007.

Antibiotic name Diseases treated: Severe urinary m log P tract infections = -2.023

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC (6R,7R)-3-(Acetoxymethyl)-7- N/A (=O)[C@@H](c3ccccc3)N)COC(=O)C)C(=O) {[(2R)-2-amino-2- O phenylacetyl]amino}-8-oxo-5- thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C18H19N3O6S 405.426 g/mol Cephalosporins (first generation) Kefglycin, Cephaloglycin anhydrous, Cephaloglycine, Kafocin

Dipole Moment (Debye) Molecular Volume Surface Area 4.48 Debye 374.64 Å3 405.36 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 119.860 Å2 3577-01-3 0.012 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 4 10

References and summary a. MOA: Cefaloglycin is effective against bacteria by inhibiting cell wall synthesis. (Walker, C. B. (1996), Selected antimicrobial agents: mechanisms of action, side effects and drug interactions. Periodontology 2000, 10: 12–28.)

b. Source: Cefaloglycin is synthesized from Cephalosporium sp. (Volpato, G, R C Rodrigues, and R Fernandez-Lafuente. "Use Of Enzymes In The Production Of Semi-Synthetic Penicillins And Cephalosporins: Drawbacks And Perspectives." Current Medicinal Chemistry 17.32 (2010): 3855- 3873.)

c. Cell line Test (MIC) : Cefaloglycin was used to treat growing Bacillus licheniformis cells. The study was unable to determine a MIC which lead to the assumption that there are other factors to be considered to account for the variation in concentrations in the different trials. (Lepage, S, et al. "Saturation Of Penicillin-Binding Protein 1 By Beta-Lactam Antibiotics In Growing Cells Of Bacillus Licheniformis." Molecular Microbiology 16.2 (1995): 365-372.)

d. Human clinical trials : This trial analyzed the urine in order to determine how much of cephaloglycin is excreted; in particular this study observed the average in human males. (Haginaka, J, T Nakagawa, and T Uno. "Chromatographic Analysis And Pharmacokinetic Investigation Of Cephaloglycin And Its Metabolites In Man." The Journal Of Antibiotics 33.2 (1980): 236-243.)

e. Review Article: This article reviews the physicochemical properties, and route of degradation of cephalosporins. (Krimpen, P., W. Bennekom, and A. Bult. "Penicillins And Cephalosporins." Pharmaceutisch Weekblad 9.1 (1987): 1.)

Antibiotic name: Diseases treated: m log P= Cefaloram Pneumonia, Bronchitis -0.667

SMILES: IUPAC: MIC values CC(=O)OCC1=C(N2[C@@H]([C@@H](C2= (6R,7R) -3-(Acetoxymethyl)-8-

O)NC(=O)CC3=CC=CC=C3)SC1)C(=O)O oxo-7-[(phenylacetyl)amino]-5-

thia-1-azabicyclo[4.2.0]oct-2-

ene-2-carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C18H18N2O6S, 390.417 g/mol Cephalosporins Is not classified yet so it has no trade name.

Dipole Moment (Debye)= Molecular Volume= Surface Area= 4.00 Debye 326.65 Å3 393.88 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 113.011 Å2 859-07-4 0.0122 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N): atoms): 2 8

References and summary a. MOA: Since cefaloram is in the group of Cephalosporins, it’s mechanism of action is to prevent the cell wall synthesis by binding to penicillin. Penicillin is an enzyme binding proteins (PBPs) and they are essentially for the synthesis of the bacterial cell wall. (Gu, Yu Gui, et al. "1, 2, 4-oxadiazole and 1, 2, 4-thiadiazole beta-lactamase inhibitors." U.S. Patent Application 13/853,506.)

b. Source: Cefaloram is in the class of Cephlosporins , cephlosporins was first isolated from cultures of Cephalosporium acremonium (Podolsky, M. Lawrence (1998) Cures Out of Chaos: How Unexpected Discoveries Led to Breakthroughs in Medicine and Health, Harwood Academic Publishers)

c. Cell line Test (MIC):

d. Human clinical trials: A clinical trial carried to target NO-Donor for dispersing bacterial biofilms. In this clinical it was reasoned that the could be created which selectively release an No-donor upon reaction with biofilm β- lactamases ane of the antibiotic that was targeted In this clinical was cefaloram.( Barraud, Nicolas, et al. "Cephalosporin‐3′‐diazeniumdiolates: Targeted NO‐Donor Prodrugs for Dispersing Bacterial Biofilms." Angewandte Chemie 124.36 (2012): 9191-9194.)

e. Review Article: Gu, Yu Gui, et al. "1, 2, 4-oxadiazole and 1, 2, 4-thiadiazole beta-lactamase inhibitors." U.S. Patent Application 13/853,506. Podolsky, M. Lawrence (1998) Cures Out of Chaos: How Unexpected Discoveries Led to Breakthroughs in Medicine and Health, Harwood Academic Publishers. Barraud, Nicolas, et al. "Cephalosporin‐3′‐diazeniumdiolates: Targeted NO‐Donor Prodrugs for Dispersing Bacterial Biofilms." Angewandte Chemie 124.36 (2012): 9191-9194 f.

Antibiotic name Diseases treated staphylococcal m log P Cefaloridine (Cephaloradine) and streptococcal infection, UTI, Lower =-5.388 Respiratory Infections

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(= (6R,7R)-8-oxo-3-(pyridin-1-ium-1- 15 μg/ml or more for inhibition for O)Cc3sccc3)C[n+]4ccccc4)C([O-])=O ylmethyl)- G-resistant Staphylococcus aureus 7-[(2-thiophen-2-ylacetyl)amino]-5- thia-1-

azabicyclo[4.2.0]oct-2-ene-2- carboxylate

Emp. Formula, Molar mass Antibiotic group Trade names

C19H17N3O4S2, 415.486 g/mol Cephalosporin Cephalin, Ceporan

Dipole Moment (Debye) Molecular Volume Surface Area 3 4.2 Debye 340.574 A3 403.40 A

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 3 93.42A2 50-59-9 0.0123 Debye/A

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 7 1

References and summary MOA. is bactericidal against many gram-positive and gram-negative bacteria. It is also affects many renal functions in animals. For example, nephron transport and renal tubular necrosis. (Child, K. J., and M. G. Dodds. "Mechanism Of Urinary Excretion Of Cephaloridine And Its Effects On Renal Function In Animals." British Journal of Pharmacology and Chemotherapy 26.1 (1966): 108-19. Print) a.

b. Source Cephaloridine (or cefaloridine) is a first generation semisynthetic derivative of cephalosporin C. It is analogous, because it is synthesized by the displacement of celphalothin by pyridine. (Spencer, John L., Fai Y. Siu, Bill Grinnell Jackson, Harvey M. Higgins, and Edwin H. Flynn. "Chemistry of Cephalosporin Antibiotics. IX. Synthesis of Cephaloridine." The Journal of Organic Chemistry 32.2 (1967): 500-01. Print.) c. Cell line Test Anion transporter 1 (OAT1) in G-resistant Staphylococcus aureus. (Takeda, Michio, et al. "Role of organic anion transporter 1 (OAT1) in cephaloridine (CER)-induced nephrotoxicity." Kidney international 56.6 (1999): 2128-2136.)

(MIC) 2 μg/ml against all of 100 strains of penicillin G-resistant Staphylococcus aureus, with the use of a large inoculum (Only 50% were susceptible). 15 μg/ml was needed for inhibition. (Benner, Ernest J., et al. "Inactivation of cephalothin and cephaloridine by Staphylococcus aureus." Journal of bacteriology 90.6 (1965): 1599-1604.) d. Human clinical trials A clinical trial was carried out to determine the excretion of cephaloridine in patients with renal impairment. (Kunin, Calvin M., and Nuzhet Atuk. "Excretion of cephaloridine and cephalothin in patients with renal impairment." New England Journal of Medicine 274.12 (1966): 654-656.) e.

Review Article (FISHER, LARRY S., et al. "Cephalothin and Cephaloridine Therapy for Bacterial MeningitisAn Evaluation." Annals of internal medicine 82.5 (1975): 689-693.)

Kelkar, Pramod S., and James T-C. Li. "Cephalosporin allergy." New England Journal of Medicine 345.11 (2001): 804- 809.

Nolan, G., et al. "Antibiotic prophylaxis in cystic fibrosis: inhaled cephaloridine as an adjunct to oral cloxacillin." The Journal of pediatrics 101.4 (1982): 626-630. f.

Antibiotic name: Diseases treated: Bacterial m log P= Cefamandole infections of skin and bones. -0.472

SMILES: IUPAC: MIC values: [H][C@]12SCC(CSC3=NN=NN3C)=C(N1C(= (6R,7R) -7-[(2R)-2-hydroxy-2- 0.12 µg/mL -400 µg/mL against

O)[C@H]2NC(=O)[C@H](O)C1=CC=CC=C1) phenylacetamido]-3-{[(1-methyl- Escherichia coli, 0.06 µg/mL->16 µg/mL

C(O)=O 1H-1,2,3,4-tetrazol-5- against Haemophilus influenza, 0.1

yl)sulfanyl]methyl}-8-oxo-5-thia- µg/mL-12.5 µg/mL against

1-azabicyclo[4.2.0]oct-2-ene-2- Staphylococcus aureus carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C18H18N6O5S2, 462.513 g/mol Cephlosporins former Mandol

Dipole Moment (Debye)= Molecular Volume= Surface Area= 1.42 Debye 369.16 Å3 443.47 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 150.544 Å2 34444-01-4 0.0038 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N): atoms): 3 8

References and summary a. MOA: Since cefamandole is a Cephlosporins , it’s mechanism of action is to bind to specific penicillin binding proteins that is located inside the bacterial cell wall. This causes the inhibition of the third and the last stage of the bacterial cell wall synthesis which then the cell lysis is mediated by the bacterial cell wall autolytic enzymes. (Yotsuji, A., et al. "Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis." Antimicrobial agents and chemotherapy 32.12 (1988): 1848- 1853.) b. Source: Cefamandole can be prepared from an alkali metal and ammonium salt. (Chou, Ta Sen, and Gary D. Zintgraff. "Process for preparing pure cefamandole from alkali metal and ammonium salts thereof." U.S. Patent No. 4,115,644. 19 Sep. 1978.)

c. Cell line Test (MIC): In this cell line test a rabbit kidney cell line LLC-RK1 was tested for its ability to discriminate the toxicity of six cephlosporins antibiotics according to their in vitro nephrotoxic potentials in rabbits.( Williams, P. D., et al. "Comparative toxicities of cephalosporin antibiotics in a rabbit kidney cell line (LLC-RK1)." Antimicrobial agents and chemotherapy 32.3 (1988): 314-318.)

d. Human clinical trials: This clinical trial was carried out for antibiotic prophylaxis in cardiac operations using cefamandole. (Townsend, T. R., et al. "Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations." The Journal of thoracic and cardiovascular surgery 106.4 (1993): 664.)

e. Review Article: Yotsuji, A., et al. "Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin- binding proteins in Bacteroides fragilis." Antimicrobial agents and chemotherapy 32.12 (1988): 1848-1853. Chou, Ta Sen, and Gary D. Zintgraff. "Process for preparing pure cefamandole from alkali metal and ammonium salts thereof." U.S. Patent No. 4,115,644. 19 Sep. 1978. Williams, P. D., et al. "Comparative toxicities of cephalosporin antibiotics in a rabbit kidney cell line (LLC-RK1)." Antimicrobial agents and chemotherapy 32.3 (1988): 314-318. Townsend, T. R., et al. "Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations." The Journal of thoracic and cardiovascular surgery 106.4 (1993): 664. f.

Antibiotic name Diseases treated m log P Cefaparole Antibacterial infections =-1.921

SMILES IUPAC MIC values [C@H]12SCC(=C(N1C(=O)[C@H]2 (6R,7R)-7-[[2-amino-2-(4- >50µg/mL for detecting β-lactumase NC(=O)C(N)C3=CC=C(O)C=C3)C(= hydroxyphenyl)acetyl]amino]-3- O)O)CSC4=NN=C(S4)C [(5-methyl-1,3,4-thiadiazol-2- yl)sulfanylmethyl]-8-oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C19H19N5O5S3 Mass 493.579 g/mol Cephalosporin Not found

Dipole Moment (Debye) Molecular Volume Surface Area 6.44 Debye 427.64 Å3 138.024Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 158.741 Å2 51627-20-4 0.0150 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 5 10

References and summary a. MOA The Mechanism of Action is binding to the β-lactumases by using the Cephalosporin as a substrate.( .(Waxman D.J., Penicillin-Binding Proteins and the Mechanism of Action of Beta-Lactam Antibiotics, Ann Rev Biochem, Vol. 52,pg.825-869, July 1983)

b. Source The drug is derived from the fungus Acremoniun. ( Gutiérrez, S. A. N. T. I. A. G. O., et al. "Characterization of the Cephalosporium acremonium pcbAB gene encoding alpha-aminoadipyl-cysteinyl- synthetase, a large multidomain peptide synthetase: linkage to the pcbC gene as a cluster of early cephalosporin biosynthetic genes and evidence of multiple functional domains." Journal of bacteriology 173.7 (1991): Page 2354

c. Cell line Test (MIC)>50µg/mL when tested using substrated of Cephalosporins.( O'Callaghan, Cynthia H., et al. "Novel method for detection of β-lactamases by using a chromogenic cephalosporin substrate." Antimicrobial Agents and Chemotherapy 1.4 (1972): Page 233

d. Human clinical trials Study of Concentration and Antimicrobial Activity of Antibiotics Used for Catheter-Related Infections (CONAn). The test was used to on 30 patients using different Celphalosporin drugs to see what was the most effective. It is currently recruiting for phase 4.

e. Review Article Treatment of bacterial meningitis (Quagliarello, Vincent J., and W. Michael Scheld. "Treatment of bacterial meningitis." New England Journal of Medicine 336.10 (1997): 708-716.) The article is about using various Cephalosporin drugs to treat bacterial meningitis.

Antibiotic name: Diseases treated: m log P: Cefapirin Blood Infection caused by -0.368 S Bi

SMILES: IUPAC: MIC values: O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R) - 3 -[(acetyloxy)methyl]-8- Staphylococcus aureus was inhibited by

=O)CSc3ccncc3)COC(=O)C)C(=O)O oxo-7-[2-(pyridin-4- cephapirin concentrations of 0.09 to

ylsulfanyl)acetamido]-5-thia-1- 12.5 μg/ml.

azabicyclo[4.2.0]oct-2-ene-2-

carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names :

Cephalosporins (first Cefadyl C 17 H17N3O6S2 423.470 g/mol generation)

Dipole Moment (Debye): Molecular Volume: Surface Area: 4.08 debye 340.622 Å3 411.22 Å2

Surface Area (TPSA): CAS Number: D/V (dipoe moment/volume): 2 3 125.903 Å 21593 -23-7 83.5 debye/ Å

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N): atoms): 2 9

References and summary a. MOA: The bactericidal activity of cephapirin results from the inhibition of cell wall synthesis via affinity for penicillin-binding protein. (http://www.drugbank.ca/drugs/DB01139 (Drug Bank)

b. Source It is derived biosynthetically from 7-aminocephalosporanic acid

c. Cell line Test (MIC): Staphylococcus aureus was inhibited by cephapirin concentrations of 0.09 to 12.5 μg/ml. (Axelrod, Judith, Burt R. Meyers, and Shalom Z. Hirschman. "Cephapirin: in vitro antibacterial spectrum." Applied microbiology 22.5 (1971): 904-908.

d. Human clinical trials: Human clinical trials was carried out in 5 cases of reversible cephapirin-induced neutropenia were observed in 132 patients receiving this antibiotic (Pan, C. V., et al. "Cephapirin-induced neutropenia." Chemotherapy 35.6 (1989): 449-453.)

e. Review Article: Simonet M, Herrmann JL, Gehanno P, Veron M: [Activity of cefapirin against bacterial strains isolated from acute otitis media in children]. Pathol Biol (Paris). 1990 May;38(5):352-4. Pubmed: 2114604 Link_out. http://www.drugbank.ca/drugs/DB01139 Axelrod, Judith, Burt R. Meyers, and Shalom Z. Hirschman. "Cephapirin: in vitro antibacterial spectrum." Applied microbiology 22.5 (1971): 904-908 Pan, C. V., et al. "Cephapirin-induced neutropenia." Chemotherapy 35.6 (1989): 449-453 f.

Antibiotic name Diseases treated m log P Cefatrizine Respiratory tract infection =-2.38

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( 5-Thia-1-azabicyclo(4.2.0)oct-2- 8 µg/mL when used against =O)[C@@H](c3ccc(O)cc3)N)CSc4nnnc4)C( ene-2-carboxylic acid, 7- Enterobacteriaceae =O)O ((amino(4- hydroxyphenyl)acetyl)amino)-8- oxo-3-((1H-1,2,3-triazol-4- ylthio)methyl)-, (6R- (6alpha,7beta(R*)))- Emp. Formula, Molar mass Antibiotic group Trade names Empirical formula C18H18N6O5S2, Cephalosporin Cefatrizina Molar Mass 464 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 6.33 Debye 414.03 Å3 153.049 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 174.532 Å2 0051627-14-6 0.1528 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 6 11

References and summary a. MOA The drug is used to synthesize the β-lactum.( Rholl, Drew Anders. β-LACTAM RESISTANCE MECHANISMS IN Burkholderia pseudomallei AND THE TOOLS USED FOR THEIR ELUCIDATION. Diss. Colorado State University, 2011: page 20

b. SourceThe drug is derived from the fungus (Gutiérrez, S. A. N. T. I. A. G. O., et al. "Characterization of the Cephalosporium acremonium pcbAB gene encoding alpha-aminoadipyl-cysteinyl-valine synthetase, a large multidomain peptide synthetase: linkage to the pcbC gene as a cluster of early cephalosporin biosynthetic genes and evidence of multiple functional domains." Journal of bacteriology 173.7 (1991): 2354-2365.)

c. Cell line Test (MIC) 8 ug/m Verbist, Ludo. "Comparison of the antibacterial activity of nine cephalosporins against Enterobacteriaceae and nonfermentative gram-negative bacilli." Antimicrobial agents and chemotherapy 10.4 (1976): 657-663. The test was done to test the effectiveness of various cephalosporin drugs.

d. Human clinical trialsInVitro and Clinical Studies of Cefatrizine, a New Semisynthetic Cephalosporin in phase 3. (Del Busto, Ramon, et al. "In vitro and clinical studies of cefatrizine, a new semisynthetic cephalosporin." Antimicrobial agents and chemotherapy 9.3 (1976): 397-405.)

e. Review Article Actor, Paul, et al. "Cefatrizine (SK&F 60771), a new oral cephalosporin: serum levels and urinary recovery in humans after oral or intramuscular administration–comparative study with cephalexin and cefazolin." Antimicrobial agents and chemotherapy 9.5 (1976): Page 800-803

Antibiotic name Diseases treated m log P: cefazaflur Bacterial infections = 2.788

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2 (6R,7R)-3-[(1-methyltetrazol-5- 16 μg/ml in Escherichia coli, Klebsiella, NC(=O)CSC(F)(F)F)CSc3nnnn3C)C(=O) yl)sulfanylmethyl]-8-oxo-7-([2- and . Acinetobacter

O (trifluoromethylsulfanyl)acetyl]a spp.1 mino)-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar Antibiotic group Trade names massC13H13F3N6O4S3, 470.470 g/mol first-generation cephalosporin Not found

Dipole Moment (Debye) Molecular Volume Surface Area 5.45 Debye 365.44Å3 112.294Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 130.316 52123-49-6 0.0149 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 2 13

References and summary a. MOA cefazaflur is most active cephalosporins against the Enterobacteriaceae(with the exception of )1.( . Ludo. Verbist, Comparison of the Antibacterial Activity of Nine Cephalosporins Against Enterobacteriaceae and Nonfermentative Gram-Negative Bacilli, Antimicrob. Agents ,Chemother,Vol. 10(4):657.)

b. Source derived from Terrestrial microorganisms which are structurally diverse bioactive substances (Young,W C., Marcy J. B., 2 Hee B. C., Douglas K., Drug Discovery From Natural Sources, The AAPS J., Vol. 8 (2),pg. 239-235, Jan. 2006

c. Cell line Test (MIC) 16 μg/ml in Escherichia coli, Klebsiella, and Proteus mirabilis. Acinetobacter spp.1(. Ludo. Verbist, Comparison of the Antibacterial Activity of Nine Cephalosporins Against Enterobacteriaceae and Nonfermentative Gram-Negative Bacilli, Antimicrob. Agents ,Chemother,Vol. 10(4):657.

d. Human clinical trials 7 healthy adult volunteers was tested Phase not provided(Harvengt C.,Meunier H.,Lamy,M.D., Pharmacokinetic Study of Cefazaflur Compared to Cephalothin and Cefazolin,Vol.17(2-3),pg. 128-133,March 1977.

e. Review Article f. 1. Ludo. Verbist, Comparison of the Antibacterial Activity of Nine Cephalosporins Against Enterobacteriaceae and Nonfermentative Gram-Negative Bacilli, Antimicrob. Agents ,Chemother,Vol. 10(4):657. 2. George W. C.,Gregory D., Zeleznik, D., Turck,M., Cefazaflur, a New Parenteral Cephalosporin: In Vitro Studies, Antimicrob. Agents Chemother, vol.11( 4)pg. 708-711, April 1977.

Antibiotic name Diseases treated Respiratory tract m log P Cefazedone infections due to Staph. and Strep = 0.819

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@ (6R,7R)-7-{[2-(3,5-dichloro-4- 16 µg/ml of Cefazedone was shown

H]2NC(=O)CN/3/C=C(/Cl)C(=O)C(\ oxopyridin-1-yl)acetyl]amino}- to be active against enterococci

Cl)=C\3)CSc4nnc(s4)C)C(=O)O 3-[(5-methyl-1,3,4-thiadiazol- 2-yl) sulfanylmethyl]-8-oxo-5- thia-1-azabicyclo[4.2.0] oct-2-

ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C18H15Cl2N5O5S3 First Generation Refosporene, Refosporen 548.446 g/mol Cephalosporins

Dipole Moment (Debye) Molecular Volume Surface Area 6.11 Debye 441.89 Å3 469.19 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 102.821 Å2 56187-47-4 0.0138 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 11

References and summary a. MOA Cefazedone Interfere with the synthesis of bacterial cell wall. (Mason, I.S., and Kietzamann, M., Cephalosporins-Pharmacological basis of clinical use in veterinary dermatology, Vet. Dermatol., 10, 187-192, 1999.)

b. Source Cefazedone was isolated from Cephalosporium acremonium. (Mason, I.S., and Kietzamann, M., Cephalosporins-Pharmacological basis of clinical use in veterinary dermatology, Vet. Dermatol., 10, 187-192, 1999.)

c. Cell line Test (MIC) Cefazedone was active against enterococci at 16 µg/ml (Primavesi, C.A., In Vitro studies with cefazedone, Arzneim. Forsch. 29(2a), 381-4, 1979.)

d. Human clinical trials Cefazedone was in Phase I (Cross-over study) of clinical trials to determine the tolerance levels in humans. (Pabst, J., Leopold, G., Ungethium, W., Dingeldein, E., Clinical pharmacology phase I of cefazedone, a new cephalosporin, in healthy volunteers. II. Pharmacokinetics in comparison with cefazolin, Arzneim. Forsch., 29(2a), 437-443, 1979.) e. Review Article [1]. Brown, G.R., Cephalosporin- Drug Interactions, Clin. Pharmacokinet., 24(4), 289-300, 1193. [2]. Knothe, H., Microbiological activity of cefazedone as compared to cefazolin and cephalothin, Arzneim. Forsch., 29(2a), 378-381, 1979.

Antibiotic name Diseases treated Infections of m log P Cefazolin the skin. = -1.55

SMILES IUPAC MIC values =C2N1/C(=C(\CS[C@@H]1[C@@H]2N 6R,7R)-3-{[(5-methyl-1,3,4- 0.1-1.56 µg/ml varies depending on C(=O)Cn3nnnc3)CSc4nnc(s4)C)C(=O)O thiadiazol-2-yl)thio]methyl}- microorganism. 8-oxo-7-[(1H-tetrazol-1- ylacetyl)amino]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C14H14N8O4S3, 454.52 g/mol Cephalosporin Ancef, Kefzoll

Dipole Moment (Debye) Molecular Volume Surface Area 6.51 Debyes 343.52 Å3 406.72 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 156.1 Å2 25953-19-9 0.019 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 15

References and summary a. MOA: Disrupts the synthesis of peptidoglycan in bacterial cell walls.(Cox, V., Zed, P., Once-Daily Cefazolin and Probenecid for Skin and Soft Tissue Infections, The Annals of Pharmacotherapy, Vol. 38, p. 461, 2004)

b. Source: All Cephalosporins are derived from the fungus, Acremonium spp.(Khang, Y., Study of Pure and Conjugated culture Batch Fermentation of Cephalosporium acremonium, A Thesis In Chemical Engineering, p. 2, 1986)

c. Cell line Test (MIC): The concentrations will vary with different microorgansims, 0.1 µg/ml for S. aureus and 1.56 µg/ml for E. coli. (Murakawa, T., Nishida, M., Exudate Levels and Bactericidal activity of Cefazolin in a New Local Infection System Using Rat Granulma Pouches, Antimicrobial Agents and Chemotherapy, p. 1047, 1977)

d. Human clinical trials A new parentally administered semisynthetic cephalosporin with a broad spectrum of antibacterial activity, cefazolin, has been shown to be effective in adults and children against infections caused by a variety of gram-positive and gram negative bacteria. (Gold, J., McKee, J., Ziv, D., Experience with Cefazolin: An Overall Summary of Pharmacologic and Clinical Trials in Man, The Journal of Infectious Diseases, Vol. 128, p. 415-421, 1973) e. Review Article Review of the pharmacokinetic and clinical evidence for the use of once-daily cefazolin and probenecid in the treatment of skin and soft tissue infections. (Cox, V., Zed, P., Once-Daily Cefazolin and Probenecid for Skin and Soft Tissue Infections, The Annals of Pharmacotherapy, Vol. 38, p. 458-463, 2004)

Antibiotic name Diseases treatedTreatment of m log P Cefcanel urinary tract infections = 0.257

SMILES IUPAC MIC values CC1=NN=C(S1)SCC2=C(N3[C@@H]([ (6R)-7β-[[(R)- showed good activity C@@H](C3=O)NC(=O)[C@@H](C4=C Hydroxyphenylacetyl]amino]-3- againstClostridium perfringens, C=CC=C4)O)SC2)C(=O)O [[(5-methyl-1,3,4-thiadiazol-2- Bacteroides spp. its MIC value was 1 yl)thio]methyl]-8-oxo-5-thia-1- 16 mg/l . azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C19H18N4O5S3, 478.572 g/mol Cephalosporin not found

Dipole Moment (Debye) Molecular Volume Surface Area 5.29 Debye 417.41 Å3 440.24 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 108.041 Å3 41952-52-7 0.0126 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 9 3

References and summary a. MOA It disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.(Waxman D.J., Penicillin-Binding Proteins and the Mechanism of Action of Beta-Lactam Antibiotics, Ann Rev Biochem, Vol. 52,pg.825-869, July 1983

b. Source Semisynthetic cephalosporin(Klaubert,D.,Essery,J.,Barrett J.F., New cephalosporins in development pipelines, Expert Opinion on Investigational Drugs,Vol. 3(2),Pg. 133-144,1994.

c. Cell line Test (MIC) has been tested against 153 staphylococci subdivided into the species Staphylococcus aureus, S. epidermidis sensu lato and 5. saprophyticus,with and without β-lactamase production.The concentration was 0.5 mg/l for all three species(Bergan T., Da Fonseca J., Chemotherapy,Vol. 37(1),pg.43–49,1991

d. Human clinical trials400 subjects were randomized to receive cefcanel daloxate against treatment of acute uncomplicated urinary tract infection.( Nicolle L.E.,Hoepelman A.I.M.,Floor, M., Verhoef,J., Norgard, K., Comparison of Three Days’Therapy with Cefcanel or Amoxicillin for the Treatment of Acute Uncomplicated Urinary Tract Infection, Scandinavian Journal of Infectious Diseases, Vol. 25(5) ,pg. 631-637,1993.

e. Review Article 1. Nord, C.E., Lindmark A.,Persson, I., Comparative antibacterial activity of the new cephalosporin cefcanel against anaerobic bacteria, European J. of Clin Microbiol and Infectious Diseases, Vol. 8(6), pg. 550-551, June 1989 2. Chin,N. X.,Gu, J.W., Neu,H. C., In vitro activity of cefcanel versus other oral cephalosporins, Europ. J. Clin Microbiol and Infec. Diseas., Vol. 10(8), pg. 676-682, August 1991.

Antibiotic name Diseases treated Acute upper m log P Cefcapene and lower respiratory infections = -0.214

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@ (6R,7R)-3 0.5 mg/L of Cefcapene was active

H]2NC(=O)C(=C/CC)\c3nc(sc3)N)C {[(Aminocarbonyl)oxy]methyl} against 06M092613 strain of

OC(=O)N)C(=O)O -7-{(Z)-[2-(2-amino-4- Streptococcus pneumonia thiazolyl)-1-oxo-2- pentenyl]amino}-8-oxo-5-thia- 1-azabicyclo(4.2.0)oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C17H19N5O6S2 Third-generation Cefcapene pivoxil hydrochlorid, 453.500 g/mol Cephalosporin Flomox

Dipole Moment (Debye) Molecular Volume Surface Area 3.68 Debye 399.07 Å3 436.93 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 148.937 Å2 135889-00-8 0.0092 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 10

References and summary a. MOA Similar to all the third generation Cephalosporins, Cefcapene works by inhibiting the bacterial cell wall synthesis. (Barriere, S.L., Flaherty, J.F., Third-generation cephalosporins: a critical evaluation, Clin. Pharm., 3(4), 351-373, 1984.)

b. Source Cefcapene is a semisynthetic drug. (Jiang, J.A., Zhai, J. J., Yu, X. H., Teng, X., Ji, Y.F., A Practical Synthesis of Cefcapene Pivoxil, Synthesis, 2, 207-214, 2012.)

c. Cell line Test (MIC) 0.5 mg/L of Cefcapene was active against 06M092613 strain of Streptococcus pneumonia. (Sunagawa, S., Jiro, F., Higa, F., Tateyama, M., Haranaga, S., Nakasone, I., Yamane, N., Uno, T., Comparison of drug sensitivity and genotypes of clinically isolated strains of levofloxacin-resistant Streptococcus pneumoniae obtained from Okinawa Island, the Japanese main island and Hong Kong, J. Antibiot., 64, 539-545, 2011.) d. Human clinical trials Cefcapene was in Phase III (Double-blind method) of clinical trials for Chronic Respiratory Tract Infection. (Saito, A., Hiraga, Y., Watanabe, A., Saito, A., Shrimada, K., Kobayashi, H., Odagiri, S., Miki, F., Soejima, R., Oizumi, K., Hara, K., Nakashima, M., Sasaki, S., Comparative Clinical Study of Cefcapene Pivoxil and Cefteram Pivoxil in Chronic Respiratory Tract Infections by a Double-blind Method, J. Int. Med. Res., 32, 590-607, 2004.) e. Review Article [1]. Bijie, H., Kulpradist, s., Manalaysay, M., Soebandrio, A., In vitro activity, pharmacokinetics, clinical efficacy, safety and pharmacoeconomics of ceftriaxone compared with third and fourth generation cephalosporins: review, J. Chemother., 17(1), 3-24, 2005. [2]. Thornsberry, C., Review of in vitro activity of third-generation cephalosporins and other newer beta- lactam antibiotics against clinically important bacteria, Am. J. Med., 79(2), 14-20, 1985. [3]. Barriere, S.L., Flaherty, J.F., Third-generation cephalosporins: a critical evaluation, Clin. Pharm., 3(4), 351-373, 1984.

Antibiotic name Diseases treated m log P Cefclidine gram negative and gram positive infections =-5.781

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4- 0.25-8 mg/ml, Streptococcus =O)C(=N \OC)/c3nc(sn3)N)C[N+]45CCC(C( thiadiazol-3-yl)-2- pneumoniae methoxyiminoacetyl]amino]-3-[(4- =O)N)(CC4)CC5)C([O -])=O carbamoyl-1-azoniabicyclo[2.2.2]octan- 1-yl)methyl]-8-oxo-5-thia-1- azabicyclo[4.2.0] oct-2-ene-2- carboxylate

Emp. Formula, Molar mass Antibiotic group Trade names

C21H26N8O6S2, 550.61 g/mol Cephalosporin

Dipole Moment (Debye) Molecular Volume Surface Area 7.79 Debye 484.36 Å3 509.93 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 206.034 Å2 105239-91-6 0.016 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 5 14

References and summary a. MOA Cefclidine disrupts synthesis of the peptidoglycan layer of bacterial cell walls. It has the same mode of action as other beta-lactam antibiotics. (Bryskier, A., New concepts in the field of cephalosporins: C-3′quaternary ammonium (Group IV), Clin. Micro. Inf., 3(1), p. 1-6, 1997)

b. Source Cephalopsporins were derived from the fungus, Acremonium. (Marks, M., The Cephalosporins: Are they as important as their numbers suggest, Am. J. Dis. Child, 132(12), p. 1169-1171, 1978)

c. Cell line Test (MIC) 0.25-8 mg/ml, Streptococcus pneumoniae (Garau, J., et al, Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodynamics and clinical utility, Clin. Micro. Inf., 3(1), p. 87-101, 1997)

d. Human clinical trials A human study was conducted on various fourth generation cephalosporins testing for safety and efficiency. (Garau, J., et al, Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodynamics and clinical utility, Clin. Micro. Inf., 3(1), p. 87-101, 1997)

e. Review Article In vitro studies were conducted on different fourth generation cephalosporins, including cefclidine, to test for certain variables. (Watanabe, N., et al, Comparative in-vitro activities of newer cephalosporins cefclidin, cefepime, and cefpirome against ceftazidime- or imipenem-resistant Pseudomonas aeruginosa, J. Antimicro. Chemother., 30(5), p. 633-641, 1992)

Antibiotic name Diseases treated m log P Cedaloxime and bacterial meningitis = -1.235

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@ (6R,7R)-7-(2-(2-Amino-4- ≤2 μg/ml for Haemophilus influenza H]2NC(=O)C(=N\O)/c3nc(sc3)N)CO thiazolyl)glyoxylamido)-3- C)C(=O)O (methoxymethyl)-8-oxo-5- thia-1-azabicyclo(4.2.0)oct-2- ene-2-carboxylic acid, 7(sup 2)-(Z)-oxime

Emp. Formula, Molar mass Antibiotic group Trade names C14H15N5O6S2, 413.435 g/mol Third Generation Claforan Cephalosporin

Dipole Moment (Debye) Molecular Volume Surface Area 5.59 Debye 395.49 Å3 383.34 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 142.967 Å2 80195-36-4 0.0141 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 5 11

References and summary a. MOA Inhibits the synthesis of the bacterial cell wall. (Gustaferro, C., Steckelberg, J., Cephalosporin Antimicrobial Agents and Related Compounds, Mayo Clinic Proceedings, Vol. 66, p. 1064-1073, 1991)

b. Source All Cephalosporins are derived from the fungus, Acremonium spp.(Khang, Y., Study of Pure and Conjugated culture Batch Fermentation of Cephalosporium acremonium, A Thesis In Chemical Engineering, p. 2, 1986)

c. Cell line Test (MIC) The concentrations will vary with different microorgansims, ≤2 μg/ml for Haemophilus influenza. (Jones, R., Erwin, M., Haemophilus test medium interpretive criteria for disk diffusion susceptibility tests with cefdinir, cefetamet, cefmetazole, , cefdaloxime (RU29246, HR-916 metabolite), and trospectomycin, Diagnostic Microbiology and Infectious Disease, Vol. 15, Issue 8, p. 693-701, 1992) d. Human clinical trials Overview of the laboratory tests available for assessing antimicrobial activity in research and clinical practice, and highlights the usefulness with particular reference to newer cephalosporins, which are for oral administration. (Wiedemann, B., Laboratory Testing of Cephalosporins, University of Bonn, 1995)

e. Review Article A review of antibiotics and their different purposes. ( Labu, Z., Jahan, K., Afrin, A., Glimpse of Usage of Antimicrobial and its Unwanted Effects, International Journal of Pharmacy Teaching and Practices, Vol. 4, p. 770-771, 2013)

Antibiotic name Diseases treated Soft tissue infections m log p = -0.574 Cefdinir and respiratory tract infections

SMILES IUPAC MIC values O=C2N1/C(=C(/C=C)CS[C@@H]1[C@@H] (8-[2-(2-amino-1,3-thiazol-4-yl)- H. influenzae: 0.25 to 0.5 mg/liter 2NC(=O)C(=N \O)/c3nc(sc3)N)C(=O)O 1-hydroxy-2-nitroso- S. pneumoniae: 0.25 to 0.5 mg/liter ethenyl]amino-4-ethenyl-7-oxo- 2-thia-6- azabicyclo[4.2.0]oct-4-ene-5- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

Emp. Formula: C14H13N5O5S2 Third Generation Cephalosporins Omnicef, Cefdiel

Molar mass: 395.42 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 5.16 Debye 335.27 Å3 363.40 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 158.213 Å2 91832-40-5 0.015 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 5 10

References and summary a. MOA Cefdinir shows a broad range of activity, including in vitro activity going against Gram-positive and Gram- negative aerobes. This results in the disruption of the cell wall layer in bacteria. (Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000). 2

b. Source Staphylococcus aures & Streptococcus pyogenes (Tack, KJ., Keyserling, CH., McCarty, J., Hendrick, JA., The Cefdinir Pediatric Skin Infection Study Group., Study of Use of Cefdinir versus Cephalexin for Treatment of Skin Infections in Pediatric Patients, American Society for Microbiology., 41(4), 739-742, 1997). 1

c. Cell line Test (MIC) H. Influenzae: 0.25 to 0.5 mg/liter S. pneumoniae: 0.25 to 0.5 mg/liter (Ross, GH., Hovde,LB., Ibrahim,KH., Ibrahim, YH., Rotschafer, JC., Comparison of Once-Daily versus Twice-Daily Administration of Cefdinir against Typical Bacterial Respiratory Tract Pathogens, American Society for Microbiology, 45(10), 2936-2938, 2001). 3 d. Human clinical Cefdinir (Omnicef): Phase 4, Healthy condition, Enrollment (158), Interventional Cefdinir (Omnicef): Phase 4, Acute Bacterial Sinusitis, Enrollment (271), Interventional

trials

e. Review Article 1) Tack, KJ., Keyserling, CH., McCarty, J., Hendrick, JA., The Cefdinir Pediatric Skin Infection Study Group., Study of Use of Cefdinir versus Cephalexin for Treatment of Skin Infections in Pediatric Patients, American Society for Microbiology., 41(4), 739-742, 1997. 2) Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000. 3) Ross, GH., Hovde, LB., Ibrahim, KH., Ibrahim, YH., Rotschafer, JC., Comparison of Once-Daily versus Twice-Daily Administration of Cefdinir against Typical Bacterial Respiratory Tract Pathogens, American Society for Microbiology, 45(10), 2936-2938, 2001.

Antibiotic name Cefditoren Diseases treated bronchitis, m log P 0.62 pneumonia, and tonsillitis

• SMILES IUPAC 5(7R)-7-((Z)-2-(2- MIC values MIC90 of 0.064 μg/mL O=C3N2/C(=C(/C=C\c1scnc1C)CS[ Aminothiazol-4-yl)-2- against β-lactamase–nonproducing C@@H]2[C@@H]3NC(=O)C(=N\ (methoxyimino)acetamido)-3-((Z)-2- strains and 0.5 μg/mL against β- OC)/c4nc(sc4)N)C(=O)O (4-methylthiazol-5-yl)vinyl)-8-oxo-5- lactamase–producing strains thia-1-azabicyclo[4.2.0]oct-2-ene-2- i carboxylic acide

Emp. Formula, Molar mass Antibiotic group Trade names Spectracef rd C19H18N6O5S3 506.6 g/mol Cephalosporins- 3 Generation

Dipole Moment (Debye) 2.92Debye Molecular Volume 418.71Å3 Surface Area 442.50Å2

Surface Area (TPSA) 135.44 Å2 CAS Number 104145-95-1 D/V (dipoe moment/volume) 0.007 Debye/ Å3

Rotatable # bonds 7 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 4 atoms) 11

References and summary a. MOA Since cephalosporins are bactericidal, they have the same mode of action as other beta-lactam antibiotics (such as penicillins), however they are less at risk to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls (Yasuda K, Kurashige S, Mitsuhashi S. 1980. "Cefroxadine (CGP- 9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy 18 (1): 105–10.)

b. Source It is a semi-synthetic cephalosporin antibiotic for oral administration. It is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. (Yamada, Mototsugu et al. 2007. Crystal Structure of Cefditoren Complexed withStreptococcus pneumoniae Penicillin- Binding Protein 2X: Structural Basis for Its High Antimicrobial Activity. Antimicrob. Agents Chemother. 51:3902- 3907)

c. Cell line Test Cefditoren showed excellent activity with MIC90 of 0.064 μg/mL against β-lactamase–nonproducing strains and 0.5 μg/mL against β-lactamase–producing strains. In conclusion, the excellent intrinsic activity of cefditoren suggests that it may be a good choice for the treatment of CARTIs caused by Streptococcus pneumoniae, H. influenzae, and M. catarrhalis in China, while the activity should be closely monitored. (Qiwen, Yang, et al. ND. "Antimicrobial Surveillance: In vitro activity of cefditoren and other comparators against Streptococcus pneumoniae, Haemophilus influenzae, and causing community-acquired respiratory tract infections in China."Diagnostic Microbiology & Infectious Disease 73) l (MIC) d. Human clinical The clinical and bacteriological effectiveness of intravenous (IV) ceftriaxone followed by oral cefditoren pivoxil or IV ceftriaxone for acute pyelonephritis was compared, as a result, IV ceftriaxone followed by oral cefditoren pivoxil is highly effective and well-tolerated for the treatment of acute pyelonephritis, even for uropathogens with a high proportion of quinolone-resistant strains. (Monmaturapoj, T, Montakantikul, P, Mootsikapun, P, & Tragulpiankit, P n.d., 'A prospective, randomized, double dummy, placebo-controlled trial of oral cefditoren pivoxil 400 mg once daily as switch therapy after intravenous ceftriaxone in the treatment of acute pyelonephritis', International Journal Of Infectious Diseases, 16:E843-E849) trials ® ® e. Review Article Cefditoren pivoxil (Spectracef , Meiact ) is a third-generation oral cephalosporin with a broad spectrum of activity against pathogens, including both Gram-positive and -negative bacteria, and is stable to hydrolysis by many common β-lactamases. Cefditoren pivoxil is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis and uncomplicated skin and skin structure infections (indications may differ between countries). (Wellington, K, & Curran, M 2004, 'Cefditoren Pivoxil: A Review of its Use in the Treatment of Bacterial Infections', Drugs, 64:2597-2618, Science & Technology Collection)

Antibiotic name Diseases treated m log P Cefedrolor = -1.099

SMILES IUPAC MIC values CC1=C(N2[C@@H]([C@@H](C2=O (6r,7r)-7-(((2r)-2-amino-2-(3- )NC(=O)[C@@H](C3=CC(=C(C=C3) chloro-4- O)Cl)N)SC1)C(=O)O hydroxyphenyl)acetyl)amino)- 3-methyl-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H16ClN3O5S Cephalosporin 397.839 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 5.84 Debye 346.84 Å3 371.19 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 119.807 Å2 57847-69-5 0.0168 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 7

References and summary a. MOA

b. Source

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Diseases treated m log P Cefempidone Addison’s disease = -5.827

SMILES IUPAC MIC values C1CNC(=O)C1O/N=C(/C2=CN=C(S (6R,7R)-7-{[(2E)-2-(2-Amino- 2)N)\C(=O)N[C@H]3[C@@H]4N(C3 1,3-thiazol-5-yl)-2-{[(2-oxo-3- =O)C(=C(CS4)C[N+]5=CC=CC=C5) pyrrolidinyl)oxy]imino}acetyl]a C(=O)[O-] mino}-8-oxo-3-(1- pyridiniumylmethyl)-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylate Emp. Formula, Molar mass Antibiotic group Trade names C22H21N7O6S2, 543.585 g/mol Cephalosporin N/A

Dipole Moment (Debye) Molecular Volume Surface Area 14.17 Debye 418.49 Å3 508.47 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 138.713 Å2 103238-57-9 0.0339 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 13

References and summary a. MOA Disrupts the synthesis of peptidoglycan in bacterial cell walls.(Cox, V., Zed, P., Once-Daily Cefazolin and Probenecid for Skin and Soft Tissue Infections, The Annals of Pharmacotherapy, Vol. 38, p. 461, 2004)

b. Source All Cephalosporins are derived from the fungus, Acremonium spp.(Khang, Y., Study of Pure and Conjugated culture Batch Fermentation of Cephalosporium acremonium, A Thesis In Chemical Engineering, p. 2, 1986)

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Diseases treated m log P Cefepime Pneumonia =-5.436

SMILES IUPAC MIC values

O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R,Z)- 4 and 8 μg/ml when tested for inhibition

=O)C(=N\OC)/c3nc(sc3)N)C[N+]4(C)CCCC4 7-(2-(2-aminothiazol-4-yl)-2- against Pseudomonas aeruginosa

)C([O-])=O (methoxyimino)acetamido)-

3-((1-methylpyrrolidinium-1-

yl)methyl)-8-oxo-5-thia-

1-aza-bicyclo[4.2.0]oct-2-ene-2-

carboxylate

Emp. Formula, Molar mass Antibiotic group Trade names C19H24N6O5S2, 480.56 g/mol Cephalosporins Maxipime

Dipole Moment (Debye) Molecular Volume Surface Area 4.16 Debye 413.86 Åᶾ 125.898 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 150.048 Ų 88040-23-7 0.010 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 8

References and summary a. MOA The mechanism of action is that Cefepime inhibits the synthesis of peptidoglycan in the cell wall. (Kessler, Robert E. "Cefepime microbiologic profile and update." The Pediatric infectious disease journal 20.3 (2001): 331-336.

b. Source The natural source of cefepime is the fungus Emercellopsis minimum. (Gutierrez, Kathleen. "Pharmacology review newer antibiotics: cefepime." Neoreviews 5.9 (2004): e382-e386.

c. Cell line Test (MIC) A cell line test of 4 and 8 μg/ml was carried out to test for inhibition against Pseudomonas aeruginosa. (Cappelletty, Diane M. "Evaluation of Several Dosing Regimens of Cefepime, with Various Simulations of Renal Function, against Clinical Isolates of Pseudomonas aeruginosa in a Pharmacodynamic Infection Model." Antimicrobial agents and chemotherapy 43.1 (1999): 129-133. d. Human clinical trials A clinical trial was carried out to determine the effectiveness of Cefepime and Metronidazole for treatment of intra-abdominal infections. (Barie, Philip S., et al. "A randomized, double-blind clinical trial comparing cefepime plus metronidazole with imipenem-cilastatin in the treatment of complicated intra-abdominal infections." Archives of surgery 132.12 (1997): 1294-1302.

e. Review Article A review of cefepime in children. (Blumer, Jeffrey L., Michael D. Reed, and Catherine Knupp. "Review of the pharmacokinetics of cefepime in children." The Pediatric infectious disease journal 20.3 (2001): 337-342.

Cefepime and ceftazidime was compared for effectiveness in the treatment of fever and neutropenia with cancer patients. (MUSTAFA, MAHMOUD M., et al. "Comparative study of cefepime versus ceftazidime in the empiric treatment of pediatric cancer patients with fever and neutropenia." The Pediatric infectious disease journal 20.3 (2001): 362-369.

Antibiotic name Diseases treated m log P Cefetamet Pulmonary disease, broad infections =-0.333

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-7-{[(2Z)-2-(2-amino-1,3- 0.2-1 µg/ml, S. pneumoniae =O)C(=N \OC)/c3nc(sc3)N)C)C(=O)O thiazol-4-yl)- 2-methoxyiminoacetyl]amino]-3- methyl-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C14H15N5O5S2,, 397.432 g/mol Cephalosporin Altamet, Cepime O, Kuzet

Dipole Moment (Debye) Molecular Volume Surface Area 3.22 Debye 344.42 Å3 381.27 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 147.219 Å2 65052-63-3 0.0093 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 4 10

References and summary a. MOA Ceftezole disrupts synthesis of the peptidoglycan layer of bacterial cell walls. It has the same mode of action as other beta-lactam antibiotics. (Casal, J., B-lactam activity against resistant pneumococcal strains is enhanced by the immune system, J. Antimicro. Chemother., 50(3) p. 83-86, 2002)

b. Source Cephalopsporins were derived from the fungus, Acremonium. (Marks, M., The Cephalosporins: Are they as important as their numbers suggest, Am. J. Dis. Child, 132(12) p. 1169-1171, 1978)

c. Cell line Test (MIC) 0.2-1 µg/ml, S. pneumonia (Baquero, et al., Antibiotic resistance of microorganisms involved in ear, nose, and throat infections, Ped. Inf. Dis. J., 13(1) p. 9-14, 1994)

d. Human clinical trials Cefetamet was evaluated after intravenous infusion. (Koup, J., et al., Pharmacokinetics of cefetamet (Ro 15-8074) and cefetamet pivoxil (Ro 15-8075) after intravenous and oral doses in humans, J. Antimicro. Chemother., 32(4) p. 573-579, 1988)

e. Review Article Cefetamet has shown to have promising in vitro activity against respiratory pathogens. (Bryson, H., Cefetamet Pivoxil, Drugs, 45(4), p. 589-621, 1993)

Antibiotic name Diseases treated m log p = -2.223 Cefetrizole Respiratory Tract Infections

SMILES IUPAC( MIC values Unknown c1cc(sc1)CC(=O)N[C@H]2[C@@H]3N(C2= (6R,7R)-8-Oxo-7-[2- O)C(=C(CS3)CSc4[nH]ncn4)C(=O)[O -] thienylacetylamino]-3-[(1H-s- miSMILES [O- triazol-3-ylthio)methyl]-5-thia-1- ]C(=O)C4=C(CSc1ncn[nH]1)CS[C@@H]3[C azabicyclo[4.2.0]oct-2-ene-2- @H] carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C16H15N5O4S3 Not Classified Cephalosporins Cefetrizolum Molar mass: 437.525

Dipole Moment (Debye) Molecular Volume Surface Area 2.76 Debye 376.69 Å3 408.36 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 131.11 Å2 65307-12-2 0.007 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 3 9

References and summary a. MOA Cefetrizole inhibits the cell wall synthesis. (Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000). 1

b. Source Cephalosporium acremonium (Skatrud, PL., Tietz, AJ., Ingolia, TD., Cantwell, CA., Fisher, DL., Chapman, JL., Queener, SW., Use of Recombinant DNA to Improve Production of Cephalosporin C By Cephalosporium acremonium, Nat., Biotech., 7, 477-485, 1989). 2

c. Cell line Test (MIC) Unknown

d. Human clinical trials Unknown

e. Review Article 1) Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000. 2) Skatrud, PL., Tietz, AJ., Ingolia, TD., Cantwell, CA., Fisher, DL., Chapman, JL., Queener, SW., Use of Recombinant DNA to Improve Production of Cephalosporin C By Cephalosporium acremonium, Nat., Biotech., 7, 477-485, 1989.

Antibiotic name Cefivitril Diseases treated Prophylaxis and m log P -0.798 treatment of infections caused by bacteria susceptible to Cefivitri

SMILES IUPAC (6R,7R)-7-(2-(((Z)-2- MIC values N/A Cn1c(nnn1)SCC2=C(N3[C@@H]([C@@H]( Cyanovinyl)thio)acetamido) -3-

C3=O)NC(=O)CS/C=C\C#N)SC2)C(=O)O (((1-methyl-1H-tetrazol-5-

yl)thio)methyl)-8-oxo-5-thia-1-

azabicyclo(4.2.0)oct-2-ene-2-

carboxylic acid.

Emp. Formula, Molar mass C H N O S Antibiotic group Cephalosporin- Trade names Generic Only 15 15 7 4 3 453.53 g/mol Not Classified

Dipole Moment (Debye) 3.02 Debye Molecular Volume 405.05 Å3 Surface Area 446.47 Å2

Surface Area (TPSA) 154.11 Å2 CAS Number 66474-36-0 D/V (dipoe moment/volume) 0.00745 Debye/ Å3

Rotatable # bonds 8 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 2 atoms) 11

References and summary a. MOA Since cephalosporins are bactericidal, they have the same mode of action as other beta-lactam antibiotics (such as penicillins), however they are less at risk to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls (Yasuda K, Kurashige S, Mitsuhashi S (July 1980). "Cefroxadine (CGP- 9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy 18 (1): 105–10.)

b. Source is a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as "Cephalosporium". "In patients allergic to penicillin, consider second and third generation cephalosporins for life threatening infections. BMJ 335:991–991)

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Diseases treated m log P Cefixime Bronchitis, Pneumonia = -1.053

SMILES IUPAC MIC values

O=C2N1/C(=C(/C=C)CS[C@@H]1[C@@H] (6R,7R)-7-{[2-(2-amino-1,3- •Escherichia coli: 0.015 µg/mL - 4 µg/mL

2NC(=O)C(=N\OCC(=O)O)/c3nc(sc3)N)C(= thiazol-4-yl)-2-(carboxy • Haemophilus influenzae: ≤0.004

O)O methoxyimino)acetyl]amino}-3- µg/mL - >4 µg/mL

ethenyl-8-oxo-5-thia- • Proteus mirabilis: ≤0.008 µg/mL

1-azabicyclo[4.2.0]oct-2-ene-2- - 0.06 µg/mL

carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H15N5O7S2, 453.452 g/moll Cephalosporin antibiotic Suprax

Dipole Moment (Debye) Molecular Volume Surface Area 3.1 Debye 407.41 Å3 437.88 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 184.518 Ų 79350-37-1 0.008 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 10

References and summary a. MOA The mechanism of action of cefixime, a beta-lactam antibiotic, inhibits synthesis in the bacterial cell wall. (Marshall, William F., and Janis E. Blair. "The cephalosporins." Mayo Clinic Proceedings. Vol. 74. No. 2. Elsevier, 1999.

b. Source Cefixime is a Cephalosporin antibiotic that can have bacterial resistance. (Marshall, William F., and Janis E. Blair. "The cephalosporins." Mayo Clinic Proceedings. Vol. 74. No. 2. Elsevier, 1999.

c. Cell line Test (MIC) A cell line test of 4 µg/ml was carried out to test for inhibition against Escherichia coli. (Garcia-Rodriguez, J. A. "Bacteriological comparison of cefixime in patients with noncomplicated urinary tract infection in Spain." Chemotherapy 44.Suppl.≦ 1 (1998): 28-30.

d. Human clinical trials Cefixime was very successful with the treatment of urinary tract infections in children.(Lettgen, B., and K. Tröster. "[Prophylaxis of recurrent urinary tract infections in children. Results of an open, controlled and randomized study about the efficacy and tolerance of cefixime compared to nitrofurantoin]." Klinische Padiatrie 214.6 (2001): 353- 358.

e. Review Article The composite of cefixime and amoxicillin was effective with the treatment of Penicillin-Resistant Streptococcus pneumoniae Infection. (Matsumoto, Yoshimi. "Combination cefixime/amoxicillin against penicillin-resistant Streptococcus pneumoniae infection." Chemotherapy 44.Suppl. 1 (1998): 6-9.

Treatment of urinary tract infections in adults and children with cefixime. (Fanos, V., and L. Cataldi. "Cefixime in urinary tract infections with special reference to pediatrics: overview." Journal of chemotherapy 13.2 (2001): 112- 117.

Antibiotic name Diseases treated m log P Cefmatilen gram negative and positive infections =-0.721

SMILES IUPAC MIC values C1C(=C(N2[C@H](S1)[C@@H](C2=O)NC(= (6R,7R)-7-{[(2Z)-2-(2-amino-1,3- 0.125-0.25 mg/L, Neisseria gonorrhoeae O)/C(=N \O)/C3=CSC(=N3)N)C(=O)O)SCSC thiazol-4-yl)- 2- 4=NNN=C4 (hydroxyimino)acetyl]amino}-8-oxo- 3-{[(1H-1,2,3- triazol-4- ylsulfanyl)methyl]sulfanyl}-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C15H14N8O5S4, 514.582 g/mol Cephalosporin Cegmatilen hydrochloride hydrate

Dipole Moment (Debye) Molecular Volume Surface Area 5.82 Debye 413.28 Å3 452.31 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 199.788 Å2 140128-74-1 0.014 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 6 13

References and summary a. MOA Cefmatilen disrupts synthesis of the peptidoglycan layer of bacterial cell walls. It has the same mode of action as other beta-lactam antibiotics. (Lee, D., et al, Ceftezole a cephem antibiotic, is an α-glucosidase inhibitor with in vivo anti-diabetic activity, Int. J. Mol. Med, 20(3), p. 379-383, 2007)

b. Source Cephalopsporins were derived from the fungus, Acremonium. (Marks, M., The Cephalosporins: Are they as important as their numbers suggest, Am. J. Dis. Child, 132(12) p. 1169-1171, 1978)

c. Cell line Test (MIC) 0.125-0.25 mg/L, Neisseria gonorrhoeae. (Chisholm, S., et al, Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink?, J. Antimicro. Chemother., 65(10) p. 2141-2148, 2010)

d. Human clinical trials Ceftamilen hydrochloride hydrate was tested to determine the effectiveness of the antibiotic for oral use. (Takeuchi, M., et al, Immunological properties of S-1090 cefmatilen hydrochloride hydrate, Jo. Tox. Sci., 26(1) p. 231-242)

e. Review Article Cephalosporins including cefmatilen have been studied over the past twenty years in various studies in order to determine pharmokinetics, absorbtion, and distribution of the drugs. (Craig, W., Pharmokinetic/Pharmodynamic parameters: Rationale for antimicrobial dosing of mice and men, Clin. Inf. Dis., 26(1), p. 1010, 1998)

Antibiotic name Diseases treated: Urinary tract m log P Cefmetazole infections, skin infections = -0.933

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@]2(OC)NC (6R,7S)-7-(2- Bacteroides fragilis: 0.06 µg/mL - >256 (=O)CSCC#N)CSc3nnnn3C)C(=O)O (cyanomethylthio)acetamido)-7- µg/mL methoxy-3-((1-methyl-1H- Clostridium difficile: 8 µg/mL - >128 tetrazol-5-ylthio)methyl)-8-oxo- µg/mL 5-thia-1-azabicyclo[4.2.0]oct-2- Staphylococcus aureus: 0.5 µg/mL - 256 ene-2-carboxylic acid µg/mL

Emp. Formula, Molar mass Antibiotic group Trade names nd C15H17N7O5S3 471.538 g/mol Cephalosporin (2 generation) Zefazone

Dipole Moment (Debye) Molecular Volume Surface Area 5.10 Debye 402.83 Å3 443.49 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 135.297 Å2 56796-20-4 0.013 debeye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 2 15

References and summary a. MOA: Cefmetazole is effective against bacteria by inhibiting cell wall synthesis. (Walker, C. B. (1996), Selected antimicrobial agents: mechanisms of action, side effects and drug interactions. Periodontology 2000, 10: 12–28.)

b. Source: Cefmetazole is synthesized from Cephalosporium sp. (Volpato, G, R C Rodrigues, and R Fernandez-Lafuente. "Use Of Enzymes In The Production Of Semi-Synthetic Penicillins And Cephalosporins: Drawbacks And Perspectives." Current Medicinal Chemistry 17.32 (2010): 3855- 3873.)

c. Cell line Test (MIC) : The activity of cefmetazole is compared against Neisseria gonorrhoeae. The MIC was determined to range from 0.125 µg/ml and 0.25 µg/ml. (Li, Lan-Hui, et al. "Non-Cytotoxic Nanomaterials Enhance Antimicrobial Activities Of Cefmetazole Against Multidrug-Resistant Neisseria Gonorrhoeae." Plos ONE 8.5 (2013): 1-10.)

d. Human clinical trials : Patients who had undergone surgery for colorectal cancer were treated with cefmetazole sodium in order to analyzes the pharmacokinetics of cefmetazole in serum, intestinal tissue, and and subcutaneous adipose tissue. (Nakamura, Takatoshi, et al. "Tissue Concentrations Of Antibiotics Given Prophylactically During Colorectal Cancer Surgery." Hepato-Gastroenterology 60.126 (2013): 1371-1375)

e. Review Article: This article examines the effectiveness in using cefmetazole to treat patients with urinary tract infections caused by extended spectrum beta-lactamase-producing organisms. (Asako, Doi, et al. "The Efficacy Of Cefmetazole Against Pyelonephritis Caused By Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae." International Journal Of Infectious Diseases 17.(n.d.): e159-e163.)

Antibiotic name Diseases treated m log P Cefodizime Gonorrhea, Pneumonia = 0.219

SMILES IUPAC MIC values

O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol- 0.03 µg/mL, Streptococcus pneumoniae

=O)C(=N\OC)/c3nc(sc3)N)CSc4nc(c(s4)CC( 4-yl)-2- methoxyiminoacetyl]amino}-3-{[5- =O)O)C)C(=O)O (carboxymethyl)-

4-methyl-1,3-thiazol-2- yl]sulfanylmethyl}-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C20H20N6O7S4, 584.67 g/mol Third-generation cephalosporins Newdizime

Dipole Moment (Debye) Molecular Volume Surface Area 2.90 Debyes 494.60 Å3 543.83 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 197.41 Å2 69739-16-8 0.0059 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N) atoms) 5 13

References and summary a. MOA: Inhibit synthesis of the cell wall of bacteria. [Sykes, R., Bush, K., Interaction of new cephalosporins with β- lactamases and β-lactamase-producing gram-negative bacilli, Reviews Infect. Dis., 5(supplement 2), pp. S356-S367, 1983]

b. Source: Cefodizime is synthesized from cephalosporin C. [Auda, S., Mrestani, Y. Nies,D.,Grobe, C., Neubert, R., Preparation, physicochemical characterization and biological evaluation of cefodizime metal ion complexes, J. Pharm. Pharmac., 61(1), pp. 1-6, 2009]

c. Cell line Test (MIC): Against Streptococcus pneumoniae, cefodizime inhibits its growth at a minimum concentration of 0.03 µg/mL. [Georgopoulos, A., Buxbaum, A., Straschil, U., The Austrian Bacterial Surveillance Network, Graninger, W., Austrian national survey of prevalence of antimicrobial resistance among clinical isolates of Streptococcus pneumoniae 1994-96, Scand. J. Infect. Dis., 30(1), pp. 345-349, 1998]

d. Human clinical trials: At Sacré-Coeur Hospital, a patient went into anaphylactic shock from cefodizime. [Romano, A., Viola, M., Guéant-Rodriguez, R., Valluzzi, R., Guéant, J., Selective immediate hypersensitivity to cefodizime, Allergy, 60(1), pp. 1544-1545, 2005]

e. Review Article: This article provides information about cefodizime’s antibacterial activity, uses, history, and properties. [Barradell, L., Brogden, R., Cefodizime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use, Drugs, 44(5), pp. 800-834, 1992]

Antibiotic nameCefonicid Diseases treated Pneumonia and m log P Sepsisi -3.402

SMILES O=C2N1/C(=C(\CS[C@@H]1[C@ IUPAC6R,7R)-7-[(2R)-2-hydroxy- MIC values0.30-16 µg/ml, Escherichia @H]2NC(=O)[C@H](O)c3ccccc3)CSc4nnn 2-phenylacetyl)amino]-8-oxo- Coli. n4CS(=O)(=O)O)C(=O)O 3-{[1-(sulfomethyl)tetrazol-5- yl]sulfanylmethyl}- 5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic groupSecond Trade namesGideon, Monocid C18H18N6O8S3, 542.569 g/mol Generation Cephalosporins

Dipole Moment (Debye) 6.21 Debye Molecular Volume408.85 Å3 Surface Area453.21 Å2

Surface Area (TPSA) 204.914 Å2 CAS Number61270-58-4 D/V (dipoe moment/volume)0.016 Debye/ Å3

Rotatable # bonds9 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)4 atoms)14

References and summary a. MOA Cefonicid is similar to the penicillins, as they are both beta-lactam antibiotics. By binding to specific penicillin-binding proteins inside the bacterial cell wall, cefonicid inhibits the third and last stage of bacterial cell wall synthesis. Autolysins on the bacterial cell mediate Cell lysis. (Pontzer, R., et al. Cefonicid: a long-acting, second generation cephalosporin. Antimicrobial activity, pharmacokinetics, clinical efficacy and adverse effects. Pharmacotherapy. 4 (6); p. 325-333, 1984)

b. Source Cefonicid derives from the fungus Acremonium. (Heim-Duthoy, K., et al. Pharmacokinetics of cefonicid in patients with skin and skin structure infections. Antimicrobial Agents Chemotherapy. 32 (4); p. 485-487, 1988)

c. Cell line Test (MIC) 0.30- 16 µg/ml, Escherichia Coli., (Saaltiel, E., and R. N. Brogden. 1986. Activities of Cefonicid vs Escherichia coli strain in cirrhotic patients. Am. J. Med., 32(9), p.1871-1955, 1995

d. Human clinical trials This trial compared cefonicid (2g every 12 h) and ceftriaxone (2g every 24 h) for their efficacy and safety in treating spontaneous bacterial in cirrhotic patients in an open randomizied clinical trial of 30 patients per group. (Gomez-Jimenez, J., et al, Randomized trial comparing ceftaxione with cefonicid for treatment of spontaneous bacterial peritonitis in cirrhotic patients. Antimicrob, Chemother (37), p. 1587-1592,1993.)

e. Review Article(Dudley MN, Quintilliani R, Nightingale CH. A review of cefonicid, a long-aacting cephalosporin. Clinical Pharmacy, 3(1), p.23-32, 1994.)

Antibiotic name Diseases treated Respiratory Tract m log P = -1.041 Cefoperazone Infections & Urinary Tract Infections

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-7-[(2R)-2-{[(4-ethyl-2,3- Acinetobacter calcoaceticus: 16-64 =O)[C@@H](c3ccc(O)cc3)NC(=O)N4C(=O) dioxopiperazin-1-yl)carbonyl]amino}-2- µg/ml (4-hydroxyphenyl)acetamido]-3-{[(1- C(=O)N(CC)CC4)CSc5nnnn5C)C(=O)O methyl-1H-1,2,3,4-tetrazol-5- Bacteroides thetaiotaomicron: 8.0/4.0 to yl)sulfanyl]methyl}-8-oxo-5-thia-1- 32/16 µg/ml azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C25H27N9O8S2 Third Generation Cephalosporins Cefobid Molar mass: 645.68 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 4.53 Debye 572.04 Å3 610.17 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 220.26 Å2 62893-19-0 0.008 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N) atoms) 4 17

References and summary a. MOA Cefoperazone inhibits the cell wall synthesis. (Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000). 2

b. Source Bacteroides fragilis (Barry, AL., Jones, RN., The Collaborative Antimicrobial Susceptibility Testing Group., Criteria for Disk Susceptibility Tests and Quality Control Guidelines for the Cefoperazone-Sulbactam Combination, American Society for Microbiology., 26(1), 13-17, 1988). 1

c. Cell line Test (MIC) Acinetobacter calcoaceticus: 16-64 µg/ml Bacteroides thetaiotaomicron: 8.0/4.0 to 32/16 µg/ml (Barry, AL., Jones, RN., The Collaborative Antimicrobial Susceptibility Testing Group., Criteria for Disk Susceptibility Tests and Quality Control Guidelines for the Cefoperazone-Sulbactam Combination, American Society for Microbiology., 26(1), 13-17, 1988). 1 d. Human clinical trials Condition: Infection, Drug: Magnex (Sulbactabam Sodium/Cefoperazone Sodium 1:1) , Phase 4.

e. Review Article 1) Barry, AL., Jones, RN., The Collaborative Antimicrobial Susceptibility Testing Group., Criteria for Disk Susceptibility Tests and Quality Control Guidelines for the Cefoperazone-Sulbactam Combination, American Society for Microbiology., 26(1), 13-17, 1988. 2) Guay, DRP., Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin, Pediatri Infect Dis J., 19, 141-146, 2000.

Antibiotic name Diseases treated m log P Cefoselis Community-acquired pneumonia = -5.664

SMILES IUPAC MIC values CO/N=C( \C1=CSC(=N1)N)/C(=O)N[C@H]2[ (6R,7R)-3-[[3-amino-2-(2- 4 µg/mL, Escherichia coli C@@H]3N(C2=O)C(=C(CS3)C[N+]4=CC=C( hydroxyethyl)pyrazol-1-ium-1- pHSG398/NDM-1 N4CCO)N)C(=O)[O -] yl]methyl]-7-[[(2E)-2-(2-amino-1,3- thiazol-4-yl)-2- methoxyiminoacetyl]amino]-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2-ene- 2-carboxylate Emp. Formula, Molar mass Antibiotic group Trade names C19H22N8O6S2,, 522.567 g/mol Fourth- generation Wincef cephalosporins

Dipole Moment (Debye) Molecular Volume Surface Area 2.55 Debyes 461.98 Å3 502.32 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 205.118 Å2 122841-10-5 0.00552 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 6 14

References and summary a. MOA: Cefoselis inhibits cell wall synthesis. [Garau, J., Wilson, W., Wood, M., Carlet, J., Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodymanics and clinical utility, Clin. Microbiol. Infect., 3(supplement 1), pp. S87-S101, 1997]

b. Source: Cefoselis is a semisynthetic antibiotic derived from cephalosporin C. [Giamarellos-Bourboulis, E., Grecka, P., Tsitsika, A., Tympanidou, C., Giamarellou, H., In-vitro activity of FK 037 (cefoselis), a novel 4th generation cephalosporin, compared to cefepime and cefpirome on nosocomial staphylococci and gram-negative isolates, Diag. Microbiol. Infect. Dis., 36(3), pp. 185-191, 2000]

c. Cell line Test (MIC) : Cefoselis inhibits the growth of a strain of Escherichia coli at a concentration of 4 µg/mL. [Tada, T., Miyoshi-Akiyama, T., Dahal, R., Sah, M., Ohara, H., Kirikae, T., Pokhrel, B., NDM-8 metallo-β-lactamase in a multidrug-resistant Escherichia coli strain isolated in Nepal, Antimicrob. Agents chemother., 57(3), pp.2394-2396, 2013]

d. Human clinical trials: In this trial, cefoselis’s effects on infections in obstetric and gynecologic area were investigated. [Chimura, T., Hirayama, T.,Morisaki, N., Murayama, K., Sato, F., Akatsuka, K., Numazaki, M., Igarashi, Y., Clinical effects of cefoselis (CFSL) on infections in obstetric and gynecologic field and prevention of postoperative infections, Jpn. J. Antibiot., 53(11), pp. 637-641, 2000]

e. Review Article: This article reviews the activity and properties of the major fourth-generation cephalosporins including cefoselis. [Garau, J., Wilson, W., Wood, M., Carlet, J., Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodymanics and clinical utility, Clin. Microbiol. Infect., 3(supplement 1), pp. S87-S101, 1997]

Antibiotic name Diseases treated: Infections of the m log P Cefotaxiime respiratory tract, skin, urogenital system = -0.0871

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC(= (6R,7R,Z)-3-(Acetoxymethyl)-7- Haemophilus influenzae: ≤0.007 O)C(=N\OC)\c3nc(sc3)N)COC(=O)C)C(=O)O (2-(2-aminothiazol-4-yl)-2- µg/mL - 0.5 µg/mL (methoxyimino)acetamido)-8- Staphylococcus aureus: 0.781 µg/mL oxo-5-thia-1- - 172 µg/mL azabicyclo[4.2.0]oct-2-ene-2- Streptococcus pneumoniae: ≤0.007 carboxylic acid µg/mL － 8 µg/mL

Emp. Formula, Molar mass Antibiotic group Trade names rd C16H17N5O7S2, 455.47 g/mol Cephalosporin (3 generation) Claforan, Cefatam

Dipole Moment (Debye) Molecular Volume Surface Area 0.50 Debye 393.50 Å3 436.08 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 147.407 Å2 63527-52-6 0.001 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 14

References and summary a. MOA: Cefotaxime inhibits bacterial cell wall synthesis as it binds to penicillin-binding proteins. Roger, Small. “Pharmacology: Antibiotic Treatment Of Bacterial Infections Of The Respiratory Tract.” Anaesthesia & Intensive Care Medicine 9.Thoracic/physiology (n.d.): 506-510. ScienceDirect.

b. Source: N/A

c. Cell line Test (MIC): Cefotaxime used against Bartonella (Rochalimeaea) henselae which causes peliosis hepatitis and bacillary angiomatosis. MIC was found to be 8mg/L. (Wahl, Michael F., Gynheung An, and James M. Lee. “Effects of dimethyl sulfoxide on heavy chain monoclonal antibody production from plant cell culture.” Biotechnology Letters 17.5 (1995): 463-468.) d. e. Human clinical trials: Cefotaxime albumin is used in conjunction with cefotaxime in order to improve drug efficicay was evalutated treating patients with cirrhosis. (Guevara M, Terra C, Nazar A, Solà E, Fernández J, Pavesi M, Arroyo V, Ginès P. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012 Oct)

f. Review Article: This article reviews the effectiveness of cefotaxime in treating various gram-negative bacteria. (Plosker, G.L., R.H. Foster, and P. Benfield. "Cefotaxime: A Pharmacoeconomic Review Of Its Use In The Treatment Of Infections." Pharmacoeconomics 13.1 (1998): 91-106.)

Antibiotic nameCefotetan Diseases treatedUTI, abscess, m log P (bacterial infections), =-2.206

SMILESO=C2N1/C(=C(\CS[C@@H]1[C IUPAC(7S)-7-{[4-(1-amino-3- MIC values @]2(OC)NC(=O)C3S/C(S3)=C(/C(=O)N) hydroxy-1,3-dioxopropan-2-ylidene) Escherichia coli: 0.06 µg/mL C(=O)O)CSc4nnnn4C)C(=O)O 1,3-dithietane-2-carbonyl]amino}-7- methoxy- 3-[(1-methyltetrazol-5- yl)sulfanylmethyl]-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2-ene- 2-carboxylic acid

Emp. Formula, Molar mass Antibiotic groupSecond Trade namesApatef and Cefotan

C17H17N7O8S4 , 575.623 g/mol Generation Cephalosporins

Dipole Moment (Debye) Molecular Volume Surface Area 4.26 Debye 425.061 A3 511.52 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 2 219.943 A 69712-56-7 0.010 debye/A3

Rotatable # bonds9 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)15 atoms)5

References and summary a. MOAThe mechanism of action is inhibition of the enzyme vitamin K epoxide reductase and inhibition of aldehyde dehydrogenase. (Stork CM (2006). "Antibiotics, antifungals, and antivirals". In Nelson LH, Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA (eds.). Goldfrank's toxicologic emergencies. New York: McGraw-Hill. p. 847. ISBN 0-07-143763-0. Retrieved 2009-07-03.)

b. SourceCefotetan is a second generation Cephalosporin derived from the fungus Acremonium. (DeModena, J. A., et al. "The production of cephalosporin C by Acremonium chrysogenum is improved by the intracellular expression of a bacterial hemoglobin." Nature Biotechnology 11.8 (1993): 926-929.)

c. Cell line Test (MIC) Cefotetan was tested for strains of Bacteroides fragilis (β-lactamase-producers)and the MIC value was 8 mg/l. (Werner, H. "Inhibitory activity of cefotetan and other β-lactams aginst anaerobes." Journal of Antimicrobial Chemotherapy 11.suppl A (1983): 107-115).)

d. Human clinical trialsThe duration of cefotetan against Major abdominal infections (MAI) including abscess, and diffuse peritonitis was studied for 24-hour and compared with 5-day treatments in a total of 515 patients. Fabian, Timothy C., et al. "Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial." Surgery 112.4 (1992): 788- 94.)

e. Review Article(Moes, Gregory Scott, and Bruce R. MacPherson. "Cefotetan-induced hemolytic anemia: a case report and review of the literature." Archives of pathology & laboratory medicine 124.9 (2000): 1344-1346.) f. (Holzheimer, R. G., and H. Dralle. "Antibiotic therapy in intra-abdominal infections--a review on randomised clinical trials." European journal of medical research 6.7 (2001): 277-291.)

Antibiotic name Diseases treated m log P Cefoxazole =1.512

SMILES IUPAC MIC values [C@@H]12N(C(=C(COC(C)=O)CS1)C(O)=O (6R,7R)-3-(acetyloxymethyl)-7- )C(=O)[C@H]2NC(C3=C(ON=C3C4=C(C=CC [[3-(2-chlorophenyl)-5-methyl- =C4)Cl)C)=O 1,2-oxazole-4-carbonyl]amino]- 8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C21H18ClN3O7S, 491.908 g/mol Unclassified Cephalosporins Cefoxazole, Cefoxazolum, Cephoxazol, Cefoxazol,

Dipole Moment (Debye) Molecular Volume Surface Area 4.77 Debyes 434.34 Å3 467.26 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 139.043 Å2 3920-48-6 0.0110 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 10

References and summary a. MOA

b. Source

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Diseases treated m log P Cefozopran Respiratory tract infection, MRSA = -5.508

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-7-[[(2Z)-2-(5-amino- Citrobacter freundii 25µg/ml =O)C(=N \OC)/c3nc(sn3)N)Cn5c4cccn[n+]4 1,2,4-thiadiazol-3-yl)- 2- Pseudomonas aeruginosa 6.25µg/ml cc5)C([O -])=O methoxyiminoacetyl]amino]-3- (imidazo[2,3-f]pyridazin- 4-ium- 1-ylmethyl)-8-oxo-5-thia-1- azabicyclo[4.2.0] oct-2-ene-2- carboxylate Emp. Formula, Molar mass Antibiotic group Trade names th C19H17N9O5S2, 515.52 g/mol Cephalosporin (4 generation) Firstein (Japan)

Dipole Moment (Debye) Molecular Volume Surface Area 15.19 Debye 445.85 Å3 479.62 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 140.687 Å2 113356-04-9 0.034 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 3 16

References and summary a. MOA: Cefozopran inhibits the binding to the penicillin-binding protein which interferes with the final phase of peptidoglycan synthesis. (Tsuchimori, Noboru, and Kenji Okonogi. "Penicillin-Binding Protein 5 As An Inhibitory Target Of Cefozopran In Enterococcus Faecalis." Journal Of Antimicrobial Chemotherapy (JAC) 37.3 (1996): 605- 609. Environment Complete.)

b. Source: N/A

c. Cell line Test (MIC): Cefozopran was tested against Enterococcus faecalis and had a MIC of 12.5 mg/L. (Tsuchimori, Noboru, and Kenji Okonogi. "Penicillin-Binding Protein 5 As An Inhibitory Target Of Cefozopran In Enterococcus Faecalis." Journal Of Antimicrobial Chemotherapy (JAC) 37.3 (1996): 605-609. Environment Complete.)

d. Human clinical trials: Cefozopran was administed intravenously to infants with a variety of infections including respiratory tract infection, and pharynogotonsillitis. (Motohiro, Takashi, et al. "Pharmacokinetic, Bacteriological And Clinical Studies On Cefozopran In The Pediatric Field." Japanese Journal Of Antibiotics 47.11 (1994): 1589-1611. Biological Abstracts)

e. Review Article: (Rai, Jaswant, Gurpreet Kaur Randhawa, and Mandeep Kaur. "Recent Advances In Antibacterial Drugs." International Journal Of Applied & Basic Medical Research 3.1 (2013): 3-10. Academic Search Complete.)

Antibiotic nameCefpimizole Diseases treatedInflammatory m log P=-0.708 Diseases

SMILES C1C(=C(N2C(S1)C(C2=O)NC(=O)C(C IUPAC2-[1-([(6R,7R)-2-carboxy-7- MIC values 0.1 -12 µg/mL, 3=CC=CC=C3)NC(=O)C4=C(NC=N4)C(=O)O ([(2R)-2-[(5-carboxy1H--4- pneumococcal meningitis µ )C(=O)O) carbonyl)amino]-2- phenylacetyl]amino)-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3- yl]methyl)pyridin-1-ium-4- yl]ethanesulfonate

Emp. Formula, Molar massC28H26N6O10S2, Antibiotic groupThird Trade namesCefpimizole 670.67 g/mol Generation Cephalosporins

Dipole Moment (Debye)4.23 Debye Molecular Volume375.97 Å3 Surface Area435.78 Å2

Surface Area (TPSA)181.786 Å2 CAS Number84880-03-5 D/V (dipoe moment/volume)0.011 Debye/ Å3

Rotatable # bonds7 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)5 atoms)12

References and summary a. MOA Cefpimizole is a beta-lactam antibiotic. Beta-lactam antibiotics inhibit the growth of sensitive bacteria by inactivating enzymes located in the bacterial cell membrane, which are involved in the third stage of cell wall synthesis. (Hackbarth, C., et al, New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits. Antimicrobial Agents and Chemotherapy. 27 (3); p.340-342, 1985)

b. Source Cefpimizole derives from the fungus Acremonium. (Lakings, D., et al, Pharmacokinetics of cefpimizole in normal humans after single- and multiple-dose intravenous infusions. Antimicrobial Agents Chemotherapy. 26(6); p. 802–806, 1984)

c. Cell line Test (MIC) 0.1-12 µg/ml, Cefpimizole tested against pneumococcal meningitis. d. (Tauber, M., et al, New Cephalosporins Cefotaxime, Cefpimizole, BMY 28142, and HR 810 in experimental Pneumococcal Meingitis . Antimicrobial agents and Chemotherapy, 27 (3), p.340-342, 2001)

e. Human clinical trials Trial A was conducted to measure the pharmacokinetics of antibiotics in Meningitis. (Andes, D., et al, Pharmacokinetics and Pharmacodynamics of Antibiotics in Meingitis. Infectious disease clinics of North America, 13 (3), p.595-618. 1997)

f. Review Article Hara, K., Shimada, J., New antimicrobial agent series XXI: Cefpimizole. Japanese journal of antibiotics, 40 (6), p. 1108-1122. 1994)

Antibiotic nameCefpirome Diseases treatedPseudomonas m log P aeruginosa -5.333

SMILES IUPAC1-{[(6R,7R)-7-[(2E)-2-(2- MIC values Less than 16 (mg/L), CON=C(c1csc(n1)N)C(=O)NC2C3N(C2=O)C amino-1,3-thiazol-4-yl)-2- Pseudomonas aeruginosa. (=C(CS3)C[n+]4cccc5c4CCC5)C(=O)[O-] (methoxyimino)acetamido]-2- carboxylato-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3- yl]methyl}-5H,6H,7H- cyclopenta[b]pyridin-1-ium

Emp. Formula, Molar mass Antibiotic groupFourth Trade namesCefrom

C22H22N6O5S2, 514.58 g/mol Generation Cephalosporins

Dipole Moment (Debye)5.92 Debye Molecular Volume419.274 Å3 Surface Area Area211.647 Å2

Surface Area (TPSA) 153.933 Å2 CAS Number84957-29-9 D/V (dipoe moment/volume)0.014 Debye/ Å3

Rotatable # bonds7 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)3 atoms)11

References and summary a. MOA Cefpriome disrupts the synthesis of the peptidoglycan layer of bacterial cell walls. The synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins.

b. Source Cefpriome originally derived from the fungus Acremonium. (Machaka, K., Braveny, I. In vitro activity of HR-810, a new broad-spectrum cephalosporin. Eur J Clin Microbiol (2): 345–349, 1994

c. Cell line Test Less than 16 mg/L against Pseudomonas aeruginosa. (Gargalianos P, et al., “Activity of cefpirome (HR810) against Pseudomonas aeruginosa strains with characterised resistance mechanisms to β-lactam antibiotics” J. Antimicrob. Chemother. 22 (6): 841-848, 1998 (MIC)

d. Human clinical trialsA clinical trial was conducted to observe the protein binding competitiveness of cefpriome in humans and animals. (Tabata, S., Shimura, T., Maeno, T., et al. Protein binding and albumin binding competitiveness of cefpirome sulphate in human and animals. Chemotherapy (39). P. 109–114, 2009)

e. Review Article(Brewer S. C., Wunderink R. G., Jones C. B., Leeper K. V. Clinical investigations in critical care: ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest 109:1019–1029, 1996)

Antibiotic name: Diseases treated: m log P: Cefprozil Bronchitis, Ear and skin infection -1.679

SMILES: IUPAC: MIC values: O=C2N1/C(=C(/C=C/C)CS[C@@H]1[C@@ 7-[2-amino -2-(4-hydroxyphenyl)- 0.12 µg/ml when tested for In Vitro

H]2NC(=O)[C@@H](c3ccc(O)cc3)N)C(=O) acetyl]amino-8-oxo-3-prop-1- activites against S.pneumoniae,

O.O enyl-5-thia-1- 324.0µg/ml against H. influenza and

azabicyclo[4.2.0]oct-2-ene-2- 0.5µg/ml against β-lactamase.

carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C18H19N13O5S, 389.427g/mol Cephalosorins: Second Cefzil, Procet, Cronocef Generation

Dipole Moment (Debye): Molecular Volume: Surface Area: 7.60 debye 328.629 Å3 384.58 Å2

Surface Area (TPSA): CAS Number: D/V (dipoe moment/volume): 132.957 Å2 92665-29-7 0.0231 Debyes/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N): atoms): 4 6

References and summary a. MOA: Cefprozil is a beta-lactam antibiotic. It binds to specific penicillin-binding proteins located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefprozil interferes with an autolysin inhibitor. (Drug bank)

b. Source: Since cefprozil is a second generation of Cephalosporins, it is derived from the ungus Cephalosporium acremonium.

c. Cell line Test (MIC): MIC values of Cefprozil In Vitro activity against Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and Haemophilus influenza was conducted and the MIC values are0.12 µg/ml when tested for In Vitro activites against S.pneumoniae, 324.0µg/ml against H. influenza and 0.5µg/ml against β-lactamase.(Doern, Gary V., and Raymond Vautour. "In vitro activity of cefprozil (BMY 28100) and cefepime (BMY 28142) against< i> Streptococcus pneumoniae, Branhamella catarrhalis, and< i> Haemophilus influenzae, and provisional interpretive criteria for disk diffusion and dilution susceptibility tests with< i> Haemophilus influenzae." Diagnostic microbiology and infectious disease 15.7 (1992): 633-640. d. Human clinical trials: Children ages 6 months to 12 years with signs and symptoms of AOM and evidence of middle ear effusion, as confirmed by pneumatic otoscopy or tympanometry, underwent tympanocentesis and subsequent treatment with cefprozil (15 mg/kg given twice daily) for 10 days (Pichichero, Michael E., et al. "Cefprozil treatment of persistent and recurrent acute otitis media." The Pediatric infectious disease journal 16.5 (1997): 471-478.

e. Review Article: Wiseman, Lynda R., and Paul Benfield. "Cefprozil." Drugs 45.2 (1993): 295-317. Doern, Gary V., and Raymond Vautour. "In vitro activity of cefprozil (BMY 28100) and cefepime (BMY 28142) against< i> Streptococcus pneumoniae, Branhamella catarrhalis, and< i> Haemophilus influenzae, and provisional interpretive criteria for disk diffusion and dilution susceptibility tests with< i> Haemophilus influenzae." Diagnostic microbiology and infectious disease 15.7 (1992): 633-640. f. Pichichero, Michael E., et al. "Cefprozil treatment of persistent and recurrent acute otitis media." The Pediatric infectious disease journal 16.5 (1997): 471-478

Antibiotic name Diseases treated m log P Cefquinome Coliform mastitis =-5.187

SMILES IUPAC MIC values O=C4[C@@H](NC(=O)C(=N \OC)/c1csc(N) 1-[[(6R,7R)-7-[[(2Z)-(2-Amino-4- 5, 10, and 20 mg/kg in the cephalic vein n1)[C@H]5SC \C(C[n+]3cccc2CCCCc23)=C( thiazolyl)- for Beagles (Not tested in humans) (methoxyimino)acetyl]amino]-2- /N45)C([O-])=O carboxy-8-oxo- 5-thia-1-azabicyclo[4.2.0-oct-2-en-3- yl]methyl]- 5,6,7,8-tetrahydroquinolinium inner salt

Emp. Formula, Molar mass Antibiotic group Trade names

528.60 g/mol,C23H24N6O5S2 Fourth generation Cefolorin Cephalosporin

Dipole Moment (Debye) Molecular Volume Surface Area 13.3 Debye 494.97 A3 522.93 A3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 153.933 A2 84957-30-2 0.0269 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 3 11

References and summary • MOACefquinome works to inhibit cell wall synthesis. (“Farmers, doctors battle over new drug for dairy cows.” Associated Press. 5 Apr 2007.) a.

b. Source Cefquinome is an aminothiazolyl cephalosporin derivative. (Limbert, M. I. C. H. A. E. L., et al. "Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin." Antimicrobial agents and chemotherapy 35.1 (1991): 14-19.)

c. Cell line Test (MIC) Cefquinome was given in 1mg/kg increments for E. Coli mastitis in dairy cows. (Shpigel, N. Y., et al. "Efficacy of Cefquinome for Treatment of Cows with Mastitis Experimentally Induced Using< i> Escherichia coli." Journal of dairy science 80.2 (1997): 318-323.)

d. Human clinical trialsCefquinome was tested against the treatment of mastitis and respiratory disease in cattle, goats, and sheep. (Nanduri, Bindu, et al. "The transcriptional response of to three classes of antibiotics." BMC genomics 10.Suppl 2 (2009): S4.)

e. Review Article(Laven, R. A., and D. N. Logue. "Treatment strategies for digital dermatitis for the UK." The Veterinary Journal 171.1 (2006): 79-88.) f. (Sjölund, Maria, et al. "Human Salmonella infection yielding CTX-M β-lactamase, United States." Emerging infectious diseases 14.12 (2008): 1957.)

Antibiotic name Diseases treated Respiratory m log P = -0.358 Cefradine (cephradine) tract infections, Tonsillitis

SMILES IUPAC MIC values

O=C2N1/C(=C( \CS[C@@H]1[C@@ (6R,7R)-7-{[(2R)-2-amino-2- S. aureus: 3.1 µg/ml H]2NC(=O)[C@@H](C/3=C/C\C=C/ (1-cyclohexa-1,4- S. epidermidis: 32 µg/ml C\3)N)C)C(=O)O dienyl)acetyl]amino}-3- methyl-8-oxo-5-thia- 1-azabicyclo[4.2.0]oct-2-ene- 2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C16H19N3O4S Cephalosporins: First Generation Intracef, Velosef Molar mass: 349.41 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 4.94 Debye 299.381 Å3 348.58 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 112.729 Å2 38821-53-3 0.017 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 3 7

References and summary a. MOA Involved in the inhibition of bacterial cell wall synthesis. (Antignac, A., Sieradzki, K., Tomasz, A., Perturbation of Cell Wall Synthesis Suppresses Autolysis in Staphylococcus aureus: Evidence for Coregulation of Cell Wall Synthetic and Hydrolytic Enzymes, J Bacteriol., 189(21), 7573-7580, 2007). 4

b. Source Cephalosporium acremonium (Nash, CH., Huber, FM., Antibiotic Synthesis and Morphological Differentiation of Cephalosporium acremonium., Appl Microbiol., 22(1), 6-10, 1971). 3

c. Cell line Test (MIC) 1. S. aureus: 3.1 µg/ml (Miraglia, GJ., Renz, KJ., Gadebusch, HH., Comparison of the Chemotherapeutic and Pharmacodynamic Activities of Cephradie, Cephalothin, and Cephaloridine in Mice, Antimicrob. Agents Chemother., 3(2), 270-273, 1973). 1 2. S. epidermidis: 32 µg/ml (Bill, NJ., Washington II, JA., Comparison of In Vitro Activity of Cephalexin, Cephradine, and Cefaclor Antimicrob. Agents Chemother., 11(3), 470-474, 1977). 2

d. Human clinical trials The human clinical trials are unknown in the study of Operational Research Management for Children with Severe Pneumonia. The intervention of Cephradine was followed up on day 3. No study or trial phase was provided.

e. Review Article 1. Miraglia, GJ., Renz, KJ., Gadebusch, HH., Comparison of the Chemotherapeutic and Pharmacodynamic Activities of Cephradie, Cephalothin, and Cephaloridine in Mice, Antimicrob. Agents Chemother., 3(2), 270-273, 1973. 2. Bill, NJ., Washington II, JA., Comparison of In Vitro Activity of Cephalexin, Cephradine, and Cefaclor Antimicrob. Agents Chemother., 11(3), 470-474, 1977. 3. Nash, CH., Huber, FM., Antibiotic Synthesis and Morphological Differentiation of Cephalosporium acremonium., Appl Microbiol., 22(1), 6-10, 1971. 4. Antignac, A., Sieradzki, K., Tomasz, A., Perturbation of Cell Wall Synthesis Suppresses Autolysis in Staphylococcus aureus: Evidence for Coregulation of Cell Wall Synthetic and Hydrolytic Enzymes, J Bacteriol., 189(21), 7573-7580, 2007.

Antibiotic name Diseases treated m log P Cefrotil = 0.342

SMILES IUPAC MIC values C1([C@@H](NC(Cc2ccc(cc2)C=2NCCCN2) (6R,7R)-3-Methyl-8-oxo-7-[2-[4- =O)[C@@H]2N1C(=C(CS2)C)C(=O)O)=O (1,4,5,6-tetrahydropyrimidin-2- miSMILES yl)phenyl]acetylamino]-5-thia-1- CC1=C(C(O)=O)N4[C@H](SC1)[C@H](NC(= azabicyclo[4.2.0]octan-2-ene-2- O)Cc3ccc(C2=NCCCN2)cc3)C4=O carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C20H22N4O4S , 414.484 g/mol Not Classified

Dipole Moment (Debye) Molecular Volume Surface Area 4.24 Debye 395.00 Å3 409.65 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 80.417 Å2 52231-20-6 0.0107 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 3 9

References and summary a. MOA

b. Source

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Cefroxadine Diseases treated Superficial m log P -1.91 suppurative diseases

SMILES IUPAC (6R,7R)-7-{[(2R)-2-amino- MIC values MIC levels against MSSA O=C2N1/C(=C(/OC)CS[C@@H]1[C@@H]2 2-cyclohexa -1,4-dien-1- (methicillin-sensitive Staphylococcus

NC(=O)[C@@H](C/3=C/C\C=C/C\3)N)C(= ylacetyl]amino}-3-methoxy-8- aureus) >1.56 μg/mL at their highest

O)O oxo-5-thia-1-

azabicyclo[4.2.0]octane-2-

carboxylic acid

Emp. Formula, Molar mass C16H19N3O5S Antibiotic group Trade names Oraspor and Cefthan-DS st 365.405 g/mol Cephalosporins- 1 Generation

Dipole Moment (Debye) 5.62 Debye Molecular Volume 320.92 Å3 Surface Area 348.47 Å2

Surface Area (TPSA) 114.561 Å2 CAS Number 51762-05-1 D/V (dipoe moment/volume) 0.0175 Debye/ Å3

Rotatable # bonds 5 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 8 atoms) 4

References and summary a. MOA Since cephalosporins are bactericidal, they have the same mode of action as other beta-lactam antibiotics (such as penicillins), however they are less at risk to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls (Yasuda K, Kurashige S, Mitsuhashi S (July 1980). "Cefroxadine (CGP-9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy 18 (1): 105–10.)

b. Source Synthetic- It is a derivative of a structurally modified 7-amino-cephalosporanic acid. (Yasuda K, Kurashige S, Mitsuhashi S (July 1980). "Cefroxadine (CGP-9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy 18 (1): 105–10)

c. Cell line Test Antimicrobial activities were studied for 6 antibiotics, including oral cephems, as well as cefpodoxime (CPDX), cefaclor (CCL), cefroxadine (CXD), cefixime (CFIX), ampicillin (ABPC), and erythromycin (EM), against 50 strains of methicillin-sensitive Staphylococcus aureus (MSSA). Considering overall results, CPDX appeared to be the best oral antibiotic in the treatment of pediatric patients when compared with other antibiotics examined (Matsunaga, T., Hasegawa, M., Ryuno, K., Ohmayu, S., Magara, T., Kobayashi, M., & ... Kurosaka, K. 1994. On the antimicrobial activities of oral cephems against methicillin-sensitive Staphylococcus aureus isolated from children with pediatric infection. Japanese Journal Of Antibiotics, 47(5), 485-492). (MIC) d. Human clinical A total of 64 out-patients with significant urinary tract infection were randomly allocated to treatment with cefroxadine 250 mg q.i.d. or cephalexin 500 mg q.i.d. for ten days. Both drug regimes - the cefroxadine dose was half that of cephalexin - showed good activity during treatment. However, no statistically significant differences were found between the two drugs. (Hess, Jane, P. Gammelgaard, F. Rasmussen, B. Holst, and V. Frølund Thomsen. 1984. "A randomized double-blind investigation of cefroxadine (CGP 9000) versus cephalexin in urinary tract infection." Infection 12, no. 4: 270) trials e. Review Article The acid–base properties of penicillin and cephalosporin antibiotics are summarized and systematized: as a result, it is suggested to classify penicillins and cephalosporins with respect to the acid–base type (Alekseev, Vladimir G. 2010. "Acid–base properties of penicillins and cephalosporins (a review)." Pharmaceutical Chemistry Journal 44, 14-24.

Antibiotic name Diseases treated m log P Ceftaroline fosamil Bacterial pneumonia =-5.719

SMILES IUPAC MIC values O=C4N3/C(=C(/Sc2nc(c1cc[n+](cc1)C)cs2) (6R,7R)-7-[(2Z)-2-ethoxyimino- The MIC value was 0.25 µg/mL when CS[C@@H]3[C@@H]4NC(=O)C(=N \OCC)/ 2-[5-(phosphonoamino)-1,2,4- tested on methicillin-resistant c5nc(sn5)NP(=O)(O)O)C([O-])=O thiadiazol-3-yl]acetyl]amino]-3- Staphylococcus Aureus. [4-(1-methylpyridin-1-ium-4-yl)- 1,3-thiazol-2-yl]sulfanyl]-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylate Emp. Formula, Molar mass Antibiotic group Trade names C22H21N8O8PS4 Cephalosporin Teflaro, and Zinfloro 684.01 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 45.46 Debye 566.8 Å2 181.601 Å3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 223.248 Å3 400827-46-5 0.0802 Debye/ Å2

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 11 available, attached to O, S, N) atoms) 4 16

References and summary a. MOA The mechainism of action is binding to the penicillin binding protein.( Biek, Donald, et al. "Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity." Journal of antimicrobial chemotherapy 65.suppl 4 (2010): Page 9.

b. SourceThe sourc e from which the prodrug Ceftaroline fosamil is made is from Ceftaroline.( Karlowsky, James A., et al. "In vitro activity of ceftaroline against gram-positive and gram-negative pathogens isolated from patients in Canadian hospitals in 2009." Antimicrobial agents and chemotherapy 55.6 (2011): 2837-2846.)

c. Cell line Test (MIC) The MIC value is 0.25 µg/mL when tested on methicillin-resistant Staphylococcus Aureus.( Karlowsky James A., et al. "In vitro activity of ceftaroline against gram-positive and gram-negative pathogens isolated from patients in Canadian hospitals in 2009." Antimicrobial agents and chemotherapy 55.6 (2011): 2837-2846.)

d. Human clinical trials Comparative Study of Ceftaroline vs. Ceftriaxone in Adult Subjects With Community-Acquired Pneumonia (CAP). The purpose of this test was to study whether ceftaroline is effective and safe in treating community- acquired pneumonia. The study has completed Phase 3.

e. Review Article Review of ceftaroline fosamil microbiology: integrated FOCUS studies.( Critchley, Ian A., et al. "Review of ceftaroline fosamil microbiology: integrated FOCUS studies." Journal of antimicrobial chemotherapy 66.suppl 3 (2011): 45-51. The article is about the simlilarites and differences between this drug and ceftraoline from which it is derived from.

Antibiotic name Ceftazidime Diseases treated infections m log P -5.7 caused by Pseudomonas aeruginosa

• SMILES IUPAC (6R,7R,Z)-7-(2-(2- MIC valuesCeftazidime MIC50 and O=C2N1/C(=C(\CS[C@@H]1[C@ aminothiazol-4-yl)- MIC90 were 2 and 32 μg/ml, respectively @H]2NC(=O)C(=NOC(C(=O)O)(C)C 2-(2-carboxypropan-2- (sensitive ≤8 μg/ml and resistant ≥32 )c3nc(sc3)N)C[n+]4ccccc4)C([O- yloxyimino)acetamido)-8-oxo- μg/ml against Stenotrophomonas ])=O 3-(pyridinium-1-ylmethyl)-5-thia-1- maltophilia ) i aza-bicyclo[4.2.0]

oct-2-ene-2-carboxylate

Emp. Formula, Molar mass Antibiotic group Trade names Cefzim , Fortum, rd C22H22N6O7S2 546.58 g/mol Cephalosporins- 3 Generation and Fortaz

Dipole Moment (Debye) 9.90 Debye Molecular Volume 470.09 Å3 Surface Area 502.24 Å2

Surface Area (TPSA) 160.11 Å2 CAS Number 72558-82-8 D/V (dipoe moment/volume) 0.021 Debye/ Å3

Rotatable # bonds 9 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 13 atoms) 4

References and summary a. MOA Since cephalosporins are bactericidal, they have the same mode of action as other beta-lactam antibiotics (such as penicillins), however they are less at risk to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls (Yasuda K, Kurashige S, Mitsuhashi S. 1980. "Cefroxadine (CGP- 9000), an orally active cephalosporin". Antimicrobial Agents and Chemotherapy 18 (1): 105–10.)

b. Source It is an aminothiazolyl cephalosporin. ( Neu, H.C. and Labthavikul, P. 1982. Antibacterial activity and beta-lactamase stability of ceftazidime, an aminothiazolyl cephalosporin potentially active against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 21:11-18)

c. Cell line Test The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 x MIC) of ceftazidime, ciprofloxacin and azithromycin on the morphology and adherence of 29 wild-type P-fimbriated strains of Escherichia coli was studied. The greatest filamentation and the greatest loss of adherence ability occurred at 1/2 x MIC of ceftazidime. (Vranes, J., Zagar, Z, and Kurbel, S. 1996. Influence of subinhibitory concentrations of ceftazidime, ciprofloxacin and azithromycin on the morphology and adherence of P-fimbriated escherichia coli. J Chemother 8:254-60. l (MIC) d. Human clinical To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, a randomized trial in cancer patients was conducted and a randomized trial comparing ceftazidime alone with with a combination of cephalothin, gentamicin, and carbenicillin was also conducted. (Philip A. Pizzo, M.D., et al. 1986. A Randomized Trial Comparing Ceftazidime Alone with Combination Antibiotic Therapy in Cancer Patients with Fever and Neutropenia. N Engl J Med 315:552-558) trials e. Review Article The chemistry, in vitro activity, adverse effects, and clinical indications for the new third- generationcephalosporin, ceftazidime, are reviewed. Ceftazidime appears to have a unique place among the third- generation agents in the treatment of some infectious processes caused by Pseudomonas aeruginosa. (Yost, R.L., Ramphal, R. 1985. Drug Intelligence and Clinical Pharmacy, 19:509-513.)

Antibiotic name Diseases treated m log P Cefteram laryngopharyngitis, tonsillitis,bronchitis = -1.85

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R)-7-([(2Z)-2-(2-amino-1,3- The MIC values of Cefteram ranged =O)C(=N \OC)\c3nc(sc3)N)Cn4nc(nn4)C)C( thiazol-4-yl)-2- from 0.78µg/ml to 12.5µg/ml when =O)O methoxyiminoacetyl]amino)-3- testing for Staphylococcus aureus [(5-methyltetrazol-2-yl)methyl]- 8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C16H17N9O5S2, 479.49 g/mol Cephalosporins Cetlat, Somatron, Teramiron

Dipole Moment (Debye) Molecular Volume Surface Area 7.43 debye 418.75 Å3 168.94 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 190.829 Å2 82547-81-7 0.018 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 4 14

References and summary a. MOA This interfere with penicillin binding protein activity involved in the final phase of peptidoglycan synthesis (Hanaki, H., et al. Method of detecting β-lactam antibiotic induced vancomycin resistant MRSA (BIVR). International journal of antimicrobial agents. (23)1, p. 1-5, 2004).

b. Source Cefteram is a synthetic antibiotics produced by several synthetic method (Wei, F., et al. Pharmacokinetics and bioequivalence studiesof cefteram pivoxil in healthy Chinese volunteers. European journal of drug and pharmacokinetics. (34)3, p.157-162, 2009).

c. Cell line Test (MIC) The MIC values of Cefteram ranged from 0.78µg/ml to 12.5µg/ml when testing for Staphylococcus aureus (Toyonaga, Y., et al. Bacteriological, pharmacokinetic and clinical studies on cefteram pivoxil in the pediatric field]. The Japanese journal of antibiotics. (42)8, p. 1799-1814, 1989).

d. Human clinical trials Eighty one patients were treated with cefteram against several respiratory infections (Yamaki, K., et al. Clinical studies on cefteram pivoxil in the treatment of respiratory infections. The Japanese journal of antibiotics. (43)1, p.81-88, 1990).

e. Review Article This article is a review on literature done on occupoational asthma in manufacturing antibiotics. (Díaz A., Sara, et al. Occupational asthma in antibiotic manufacturing workers: case reports and systematic review. Journal of allergy, 2011).

Antibiotic name Diseases treated m log P Ceftezole gram positive bacterial infections = -1.265

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-8-oxo-7-{[2-(tetrazol-1- 100 µg/ml, Bacteroides fragilis =O)Cn3nnnc3)CSc4nncs4)C(=O)O yl)acetyl]amino}- 3-(1,3,4-thiadiazol-2- ylsulfanylmethyl)-5-thia- 1-azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C13H12N8O4S3, 440.484 g/moll Cephalosporin Ceftezol, Ceftezole, Sodium Ceftezolum

Dipole Moment (Debye) Molecular Volume Surface Area 5.09 Debye 358.26 Å3 395.64 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 156.1 Å2 26973-24-0 0.014 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 12

References and summary a. MOA Ceftezole disrupts synthesis of the peptidoglycan layer of bacterial cell walls. It has the same mode of action as other beta-lactam antibiotics. (Lee, D., et al, Ceftezole a cephem antibiotic, is an α-glucosidase inhibitor with in vivo anti-diabetic activity, Int. J. Mol. Med, 20(3), p. 379-383, 2007)

b. Source Cephalopsporins were derived from the fungus, Acremonium. (Marks, M., The Cephalosporins: Are they as important as their numbers suggest, Am. J. Dis. Child, 132(12) p. 1169-1171, 1978)

c. Cell line Test (MIC) 100 µg/ml, Bacteroides fragilis (Yotsuji, A., et al, Mechanism of action of cephalorsporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragiliis, Antimicrob. Agents Chemother., 32(12) p. 1848-1853, 1988)

d. Human clinical trials A randomized human clinical trial was conducted testing Ceftezole versus Cefazolin to evaluate their effectiveness in the treatment of respiratory and urinary tract infections. (Long, C., et al, A randomized comparative clinical study of ceftezole sodium iv. vs cefazolin sodium iv. In treatment of respiratory and urinary tract infection, Chinese Journal of Clinical Pharmacology, 4, 2002)

e. Review Article An in vitro study found that the β-lactam antibiotic ceftezole exhibited α-glucosidase inhibitory activity. (Lee, D., et al, Ceftezole, a cephem antibiotic, is an α-glucosidase inhibitor with in vivo anti-diabetic activity, Int. J. Mol. Med., 20(3) p. 379-383, 2007)

Antibiotic name: Diseases treated: m log P: Ceftibuten Chronic bronchitis and otitis -0.999 di

SMILES: IUPAC: MIC values: O=C2N1/C(=C\CS[C@@H]1[C@@H]2NC( (6R,7R) -7-([(Z)-2-(2-amino-1,3- ranged from 0·003 to >32mg/l, with a

=O)C(=C/CC(=O)O)\c3nc(sc3)N)C(=O)O thiazol-4-yl)-5-hydroxy-5- modal MIC of 0·01 mg/l: 95% of all

oxopent-2-enoyl]amino) -8-oxo- isolates had ceftibuten MIC values of ≤8

5-thia-1-azabicyclo[4.2.0]oct-2- mg/l, the sensitivity breakpoint.

ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names: -1 C15H14N4O6S2, 410.427 g.mol Cephalosporins; Third Cedax generation

Dipole Moment (Debye): Molecular Volume: Surface Area: 6.11 debye 348.73 Å3 375.33 Å2

Surface Area (TPSA): CAS Number: D/V (dipoe moment/volume): 129.219 Å2 97519-39-6 0.0175

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N): atoms): 5 10

References and summary a. MOA: Ceftibuten inhibits mucopeptide synthesis in the bacterial cell wall making in defective and asmotically unstable (Bhatnagar, Shishir, and Jagdish Chandra. "Mechanism of Action." Indian Pediatrics 36 (1999): 901-904.

b. SourceI could not find anything about the source of Ceftibuten but I come to the conclusion since it is in the group of Cephalosporins it must be derived from the fungus Cephalosporium acremonium.

c. Cell line Test: ranged from 0•003 to >32mg/l, with a modal MIC of 0•01 mg/l: 95% of all isolates had ceftibuten MIC values of ≤8 mg/l, the sensitivity breakpoint I Bragman, S. G. L., and M. W. Casewell. "The in-vitro activity of ceftibuten against 475 clinical isolates of Gram-negative bacilli, compared with cefuroxime and cefadroxil." Journal of Antimicrobial Chemotherapy 25.2 (1990): 221-236. (MIC)

d. Human clinical trials: The pharmacokinetics have been well characterized in rising single-dose and multiple-dose studies (Barr, William H., et al. "The pharmacokinetics of ceftibuten in humans." Diagnostic microbiology and infectious disease 14.1 (1991): 93-100.

e. Review Article: Bhatnagar, Shishir, and Jagdish Chandra. "Mechanism of Action." Indian Pediatrics 36 (1999): 901-904. Bragman, S. G. L., and M. W. Casewell. "The in-vitro activity of ceftibuten against 475 clinical isolates of Gram-negative bacilli, compared with cefuroxime and cefadroxil." Journal of Antimicrobial Chemotherapy 25.2 (1990): 221-236. Barr, William H., et al. "The pharmacokinetics of ceftibuten in humans." Diagnostic microbiology and infectious disease 14.1 (1991): 93-100 f.

Antibiotic name Diseases treated m log P Ceftiofur Antibacterial infections =0.312

SMILES IUPAC MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( (6R,7R)-7-[ [(2Z)-2-(2-Amino- 0.12 to< 32µg/mL for patients who are =O)C(=N \OC)/c3nc(sc3)N)CSC(=O)c4occc4 1,3-thiazol-4-yl)- 2- susceptible to Riemerella anatipestifer )C(=O)O methoxyiminoacetyl]amino]-3- (furan-2-

carbonylsulfanylmethyl)-8-oxo-

5-thia-1- azabicyclo[4.2.0]oct-2-

ene-2-carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C H N O S Mass: 532.571 g/mol Cephalosporin Ceraxel,Excede, and Naxcel 19 17 5 7 3

Dipole Moment (Debye) Molecular Volume Surface Area 9.54 Debye 402.057 485.471 Å3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 177.43 Å3 0080370-57-6 0.0327 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 4 12

References and summary a. MOAThe MOA for Ceftiofur is similar to other cephalosporins by attacking the β-lactums.( Hornish, Rex E., and S. F. Katarski. "Cephalosporins in veterinary medicine-ceftiofur use in food animals." Current topics in medicinal chemistry 2.7 (2002): 717-731)

b. SourceThe source is derived from Acremoniun fungus.( Gutiérrez, S. A. N. T. I. A. G. O., et al. "Characterization of the Cephalosporium acremonium pcbAB gene encoding alpha-aminoadipyl-cysteinyl-valine synthetase, a large multidomain peptide synthetase: linkage to the pcbC gene as a cluster of early cephalosporin biosynthetic genes and evidence of multiple functional domains." Journal of bacteriology 173.7 (1991): 2354-2365.)

c. Cell line Test (MIC)The MIC value is 0.12 to< 32µg/mL riemenrella anatipestifer.( Chang, Chao-Fu, et al. "Antimicrobial susceptibility of Riemerella anatipestifer isolated from ducks and the efficacy of ceftiofur treatment." Journal of veterinary diagnostic investigation 15.1 (2003): 26-29.)

d. Human clinical trials Randomized clinical trial to evaluate the efficacy of a 5-day ceftiofur hydrochloride intramammary treatment on nonsevere gram-negative clinical mastitis. The clinical test was to study the effectiveness of Ceftiofur on patients who are infected with gram-negative infections.

e. Review Article Ceftiofur Resistance in Salmonella enterica Serovar Heidelberg from Chicken Meat and Humans, Canada(Dutil, Lucie, et al. "Ceftiofur resistance in Salmonella enterica serovar Heidelberg from chicken meat and humans, Canada." Emerging infectious diseases 16.1 (2010): 48.) This article is about Canadians who were determined to have salmonella from eating infected chickens.

Antibiotic name Diseases treated m log P Ceftiolene active against gram - bacteria = -1.681

SMILES IUPAC MIC values CON=C(C1=CSC(=N1)N)C(=O)NC2C3 (6R,7R)-7-([(2Z)-2-(2-amino-1,3- 0.25 μg/ml tested againstHaemophilus N(C2=O)C(=C(CS3)C=CSC4=NNC(=O) thiazol-4-yl)-2- influenza 2 C(=O)N4CC=O)C(=O)O methoxyiminoacetyl]amino)-3-[(E)- 2-([5,6-dioxo-4-(2-oxoethyl)-1H-

1,2,4-triazin-3-yl]sulfanyl)ethenyl]- 8-oxo-5-thia-1-azabicyclo[4.2.0]oct- 2-ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C20H18N8O8S3, 594.60g/mol third-generation cephalosporin Excede

Dipole Moment (Debye) Molecular Volume Surface Area 6.75 498.44Å3 186.168Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 232.049 77360-52-2 0.0135 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N) atoms) 5 16

References and summary a. MOAceftiolene works by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. It disrupt the synthesis of the peptidoglycan layer of bacterial cell walls..( Williamson, R., Gutmann L., Kitzis M D., Acar J F., An evaluation of the bacteriolytic and biochemical properties of ceftiolene, J. Antimicrob. Chemother. Vol.14 (6), pg581-593. 1984.

b. Source strain of the genera Emericellopsis-Cephalosporium(Williamson, R., Gutmann L., Kitzis M D., Acar J F., An evaluation of the bacteriolytic and biochemical properties of ceftiolene, J. Antimicrob. Chemother. Vol.14 (6), pg581-593. 1984.

c. Cell line Test 0.25 μg/ml tested againstHaemophilus influenza(Rolin O., Zerial A., Bouanchaud DH., Comparative effects of 4 cephalosporins on the incorporation of tritiated diaminopimelic acid during bacterial growth, Pathol Biol,Vol. 32(5),pg.318-21.May 1984 (MIC)

d. Human clinical trials Six volunteers were given 1 g cephalexin by mouth following a 12 hr fast. Assays were carried out in batches by agar diffusion using Sarcina lutea 400E.(GOWER P. E., DASH, C. H.,Cephalexin: human studies of absorption and excretion of a new cephalosporin antibiotic, Br. J. Pharmac., Vol.37,pg. 738-747,1969.

e. Review Article 1. Williamson, R., Gutmann L., Kitzis M D., Acar J F., An evaluation of the bacteriolytic and biochemical properties of ceftiolene, J. Antimicrob. Chemother. Vol.14 (6), pg581-593. 1984. 2. Rolin O., Zerial A., Bouanchaud DH., Comparative effects of 4 cephalosporins on the incorporation of tritiated diaminopimelic acid during bacterial growth, Pathol Biol,Vol. 32(5),pg.318-21.May 1984

Antibiotic name Diseases treated Active against m log P Ceftizoxime many gram-negative bacteria = -0.881

SMILES IUPAC MIC values CO/N=C(/C1=CSC(=N1)N)\C(=O)N[ (6R,7R)-7-[[(2Z)-2-(2-amino- 0.125 to >128 µg/ml of Ceftizoxime C@H]2[C@@H]3N(C2=O)C(=CCS3 1,3-thiazol-4-yl)-2- was shown to work when tested )C(=O)O methoxyiminoacetyl]amino]- against E. coli in Mueller-Hinton 8-oxo-5-thia-1- broth azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C13H13N5O5S2 Third generation Cefizox 383.409 g/mol Cephalosporins

Dipole Moment (Debye) Molecular Volume Surface Area 3.77 Debye 327.47 Å3 367.30 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 126.776 Å2 68401-81-0 0.012 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 3 10

References and summary a. MOA Ceftizoxime disrupts the cell wall synthesis of susceptible organism like most of the Cephalosporin. (Ceftizoxime: a third-generation cephalosporin active against anaerobic bacteria, Can. Med. Assoc. J., 142(11), 1209-1212, 1990.)

b. Source Ceftizoxime is a Semisynthetic derivate of cephalosporin (Takata, N., Suginaka, H., Kotani, S., Ogawa, M., Kosaki, G., beta Lactam Resistance in Serratia marcescens: Comparison of Action of , Apalcillin, Cefazolin, and Ceftizoxime, Antimicrob. Agents Chemother., 19(3), 397-401, 1981.)

c. Cell line Test (MIC) 0.125 to >128 µg/ml of Ceftizoxime was active when tested against E. coli in Mueller-Hinton broth (Bostanoglu, E., Demirbilek, M., Aliskan, H.E., Colakglu, S., Gocmen, J.S., Interpretation of minimal inhibitory concentrations of extended spectrum beta lactamase producing Escherichia coli and Klebsiella spp. strains according to new Clinical Laboratory and Standards Institute (CLSI) criteria, Afr. J. Microbiol. Res., 7(6), 498-503, 2013.)

d. Human clinical trials Ceftizoxime is in Phase IV of clinical trials for Caesarean conditions

e. Review Article [1]. Fu, K.P., Neu, H.C., Antibacterial activity of ceftizoxime, a beta-lactamase-stabel cephalosporin, Antimicrob. Agents chemother., 17(4), 583-590, 1980. [2]. Barriere, S.L., Flaherty, J.F., Third-generation cephalosporins: a critical evaluation, Clin. Pharm., 3(4), 351-373, 1984.

Antibiotic name Diseases treated m log P Ceftobiprole severe resistant infections = -1.504

SMILES IUPAC(6R,7R)-7-[[(2Z)-2-(5- MIC values O=C3N1/C(=C( \CS[C@@H]1[C@@H]3NC( amino-1,2,4-thiadiazol-3- 1. The MIC of ceftobiprole was 1 μg/ml =O)C( \N=O)=C2/NSC(\N)=N2)/C=C4\CCN( ylidene)- 2-nitroso-1- against methicillin C4=O)[C@@H]5CCNC5)C(O)=O oxoethyl]amino]-8-oxo-3-[(E)-[2- resistant Staphylococcus aureus oxo-1-[(3R)- 3-pyrrolidinyl]-3- 2. The MIC of ceftobiprole was 0.5 pyrrolidinylidene]methyl]-5-thia- μg/ml against methicillin-susceptible S. 1- azabicyclo[4.2.0]oct-2-ene-2- aureus and Staphylococcus lugdunensis.1 carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C20H22N8O6S2 ,534.568 g/mol fifth-generation cephalosporin Zeftera Zevtera

Dipole Moment (Debye) Molecular Volume Surface Area 10.90 Debye 463.19 Å3 495.87 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 169.910 Å2 252188-71-9 0.023 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 6 14

References and summary a. MOA Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis.(Vidaillac C.,Rybak,lM.J., Ceftobiprole: First Cephalosporin with Activity Against Methicillin-Resistant Staphylococcus aureus,J. Human Pharm. Drud Therap.,Vol. 29(5),pg.511-525,May 2009.

b. Source The prodrug, ceftobiprole medocaril, is converted rapidly and almost completely to the active drug, ceftobiprole, upon infusion by type A esterases.(Murthy B.,Hoffmann, S., Pharmacokinetics and Pharmacodynamics of Ceftobiprole, an Anti-MRSA Cephalosporin with Broad-Spectrum Activity,Clin. Pharmaco.,Vol. 47(1),pg. 21- 33,January 2008.

c. Cell line Test (MIC) ceftobiprole MICs at which 90% of the isolates tested were inhibited were as follows: methicillin-resistant Staphylococcus aureus, 1 μg/ml; methicillin-susceptible S. aureus and Staphylococcus lugdunensis, 0.5 μg/ml; prevotii, 0.125 μg/ml (Goldstein E.J.C.,Citron D. M.,Merriam C.V.,Warren Y.A.,Tyrell K.L.,Fernandez H.T., In Vitro Activity of Ceftobiprole against Aerobic and Anaerobic Strains Isolated from Diabetic Foot Infections, Antimicrob. Agents Chemother., vol. 50(11),pg.3959-3962,November 2006. d. Human clinical trials 485 patients randomized 2:1 to receive ceftobiprole or to receive vancomycin plus ceftazidime. Outcomes were determined at a test-of-cure visit and were analyzed for all patients with complicated skin and skin-structure infections of major types and severity of disease.(Noel G.J.,Bagchi, P.,lanus J.,Strauss R. S., A Randomized, Double- Blind Trial Comparing Ceftobiprole Medocaril with Vancomycin plus Ceftazidime for the Treatment of Patients with Complicated Skin and Skin-Structure Infections, Clin Infect Dis.,Vol..46(5),pg. 647-655,April 2005 e. Review Article 1. Goldstein E.J.C.,Citron D. M.,Merriam C.V.,Warren Y.A.,Tyrell K.L.,Fernandez H.T., In Vitro Activity of Ceftobiprole against Aerobic and Anaerobic Strains Isolated from Diabetic Foot Infections, Antimicrob. Agents Chemother., vol. 50(11),pg.3959-3962,November 2006. 2.Amsler, K.M.,Davies, T.A.,Wenchi S.,Jacobs M.R.,Bush K., In Vitro Activity of Ceftobiprole against Pathogens from Two Phase 3 Clinical Trials of Complicated Skin and Skin Structure Infections, Antimicrob. Agents Chemother.,Vol.52(9),pg. 3418-3423,September 2008.

Antibiotic name Diseases treated m log P Ceftoxide diarrhea, , rash = -2.399

SMILES IUPAC MIC values [C@@H]12N(C(=C(COC(C)=O)C[S]1=O)C( (6R,7R)-3-(acetyloxymethyl)-7- Still being tested O)=O)C(=O)[C@H]2NC(C(/C3=CSC(=N3)N) [[(2Z)-2-(2-amino-1,3-thiazol-4- =N\OC)=O yl)-2- methoxyiminoacetyl]amino]-5,8- dioxo-5$l^{4}-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C16H17N5O8S2, 471.469 g/mol Cephalosporins None available

Dipole Moment (Debye) Molecular Volume Surface Area 3.25 debye 379.28 Å3 172.501 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 190.595 Å2 71048-88-9 0.009 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 13

References and summary a. MOA Still being tested

b. Source Still being tested

c. Cell line Test (MIC) Still being tested

d. Human clinical trials Still being tested

e. Review Article Not available

Antibiotic name Diseases treated Gonorrhea m log P Ceftriaxone and Meningitis = -1.679

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-7-{[(2Z)-2-(2-amino-1,3- 2 μg/ml for Methicillin-susceptible =O)C(=N \OC)/c3nc(sc3)N)CS\C4=N\C(=O) thiazol-4-yl)->2- Staphylococcus aureus (MSSA) C(=O)NN4C)C(=O)O (methoxyimino)acetyl]amino}-3- {[(2-methyl-5,6-dioxo-1,2,5,6- tetrahydro-1,2,4-triazin-3- yl)thio]methyl}-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C18H18N8O7S3, 554.589 g/mol Third Generation Rocephin Cephalosporin

Dipole Moment (Debye) Molecular Volume Surface Area 5.07 Debyes 465.50 Å3 509.77 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 176.909 Å2 73384-59-5 0.0109 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 5 15

References and summary a. MOA Inhibits the synthesis of the bacterial cell wall. (Gustaferro, C., Steckelberg, J., Cephalosporin Antimicrobial Agents and Related Compounds, Mayo Clinic Proceedings, Vol. 66, p. 1064-1073, 1991)

b. Source All Cephalosporins are derived from the fungus, Acremonium spp.(Khang, Y., Study of Pure and Conjugated culture Batch Fermentation of Cephalosporium acremonium, A Thesis In Chemical Engineering, p. 2, 1986)

c. Cell line Test (MIC) Cefazolin was tested for the inhibition of MSSA. (Nannini, E., et al., Inoculum Effect with Cefazolin among Clinical Isolates of Methicillin-Susceptible Staphylococcus aureus: Frequency and Possible Cause of Cefazolin Treatment Failure, Antimicrobial Agents and Chemotherapy, Vol. 53, No. 8, p. 3437-3441, 2009) d. Human clinical trials Ceftriaxone was tested as neuroprotective agent against amyotrophic lateral sclerosis. (Traynor, B., et al., Neuroprotective agents for clinical trials in ALS, The Official Journal of the American Academy of Neurology, Vol. 67, No. 1, p. 20-27, 2006)

e. Review Article The use of Ceftriaxone in the treatment of colonic diverticular disease. (Tursi, A., Papagrigoriadis, S., Review article: the current and evolving treatment of colonic diverticular disease, Alimentary Pharmacology & Therapeutics, Vol. 30, Issue 6, p. 532-546, 2009)

Antibiotic name Diseases treated m log P Cefuracetime = 0.4

SMILES IUPAC MIC values CC(=O)OCC1=C(N2C(C(C2=O)NC(=O)C(=N 7R)-7-[2-(2-Furyl)-2-[(Z)- OC)C3=CC=CO3)SC1)C(=O)O methoxyimino]acetylamino]ceph am-3-ene-4-carboxylic acid;640/1;660-1

Emp. Formula, Molar mass Antibiotic group Trade names C17H17N3O8S, 423.4 g/mol Fifth generation Cefuracetimum Cephalosporin(Unnamed Class)

Dipole Moment (Debye) Molecular Volume Surface Area 5.15 Debye 408.43 A3 457.01 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 2 3 147.749 A 39685-31-9 0.01261 Debye/A

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 2 10

References and summary a. MOA

b. Source

c. Cell line Test (MIC)

d. Human clinical trials

e. Review Article

Antibiotic name Diseases treated m log P= Cefuroixime Treats bronchitis, and gonorrhea -0.978

SMILES IUPAC(6R,7R)-3- MIC values O=C2N1/C(=C(\CS[C@@H]1[C@@H]2NC( {[(aminocarbonyl)oxy]methyl}-7- <1 mg/L for patients with against =O)C(=N \OC)\c3occc3)COC(=O)N)C(=O)O {[(2Z)-2-(2-furyl)-2- Strepoccocus agalactia infections miSMILES (methoxyimino) acetyl]amino}-8- CO/N=C(/C(=O)N[C@H]2[C@H]1SCC(COC oxo-5-thia-1- (N)=O)=C(C(O)=O)N1C2=O)c3ccco3 azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names

C16H16N4O8S, Mass 424.390 g/mol Cephalosporin Zinacef

Dipole Moment (Debye) Molecular Volume Surface Area 5.94 Debye 334.95 Å3 400.02 Å3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 173.772 Å2 64544-07-6 0.0177 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 12

References and summary a. MOAAntibiotic used part of chemotherapeutic agent used to inhibit or kill bacteria. (Al-Gheethi, Adel AS, et al. "Biosorption of heavy metals and cephalexin from secondary effluents by tolerant bacteria." Clean Technologies and Environmental Policy 16.1 (2014): 137-148.)

b. SourceThe natural source for Cefuroxime is Strepoccocus agalactia Neu, H. C., N. J. Meropol, and K. P. Fu. "Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase-stable cephalosporin." Antimicrobial Agents and Chemotherapy 19.3 (1981): 414-423.

c. Cell line Test (MIC) TestThe lowest limit tested against Strepoccocus agalactia is ,<1 mg/ L (Wootton, M., et al. "In-vitro activity of HMR 3647 against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and β-haemolytic streptococci." Journal of Antimicrobial Chemotherapy 44.4 (1999): 445- 453.)

d. Human clinical trials Ampicillin/Sulbactam versus Cefuroxime as Antimicrobial Prophylaxis for Cesarean Section. The trial was to test what had a greater prevention of postcesarean infectious morbidity. The trial was completerd after phase 4.

e. Review Article Fast dissolving Drug delivery system : Review Article. This article discusses the effects of cefuroxime once it has been digested. (Kumari, Sunita. "Fast Dissolving Drug Delivery System: Review Article." Journal Of Pharmacy Research 3.6 (2010): 1444-1449. Academic Search Complete. Web. 19 Feb. 2014)

Antibiotic name Diseases treated m log P Cefuzonam prevent bacterial infections = -0.004

SMILES IUPAC MIC values CON=C(C1=CSC(=N1)N)C(=O)NC2C3 (6R,7R)-7-([(2Z)-2-(2-amino- In children Streptococcus pneumonia N(C2=O)C(=C(CS3)CSC4=CN=NS4)C(= 1,3-thiazol-4-yl)-2- was 0.05 µg/ml O)O methoxyiminoacetyl]amino)-8- Staphylococcus aureus was 0.39 µg/ml oxo-3-(thiadiazol-5- Enterococcus faecalis was 6.25 µg/ml1 ylsulfanylmethyl)-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2- carboxylic acid Emp. Formula, Molar mass Antibiotic groupsecond Trade names C16H15N7O5S4 ,513.59 g/mol generation cephalosporin Not found

Dipole Moment (Debye) Molecular Volume Surface Area 7.76 Debye 413.93 Å3 435.98 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 173.003 82219-78-1 0.0177 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 12

References and summary a. MOA penicillin binding proteins inhibitor(Matsumoto T, Kubo S, Haraoka M, Takahashi K, Tanaka M, Sakumoto M, Kumazawa J., Combination chemotherapy for infections due to methicillin-resistant Staphylococcus aureus with combination therapy by cefuzonam and fosfomycin or minocycline in the urologic field,Clin. Therap,Vol. 15(5),pg.819-828.

b. Source strain of the genera Emericellopsis-Cephalosporium(Mochizuki, Y., Ohkubo, H., Yoshida,A., Mayumi, M., Mikawa, H., Fundamental and clinical studies of cefuzonam in pediatrics,jpn j of antibiot,Vol.40(2)pg.385-395

c. Cell line Test (MIC)In Children , Streptococcus pneumonia was 0.05 µg/ml, Staphylococcus aureus was 0.39 µg/ml, Enterococcus faecalis was 6.25 µg/ml(Mochizuki, Y., Ohkubo, H., Yoshida,A., Mayumi, M., Mikawa, H., Clinical evaluation of cefuzonam in children, Jpn J Antibiol,Vol. 40(2),pg. 397-404,Feb. 1987.

d. Human clinical trialsMICs against 451 clinical isolates of Staphylococcus aureus were determined.( Mochizuki, Y., Ohkubo, H., Yoshida,A., Mayumi, M., Mikawa, H., Fundamental and clinical studies of cefuzonam in pediatrics,Jpn j of antibiot Vol. 40(2),pg.385-395,

e. Review Article 1. Mochizuki, Y., Ohkubo, H., Yoshida,A., Mayumi, M., Mikawa, H.,Clinical evaluation of cefuzonam in children, Jpn J Antibiol,Vol. 40(2),pg. 397-404,Feb. 1987. 2. Mochizuki, Y., Ohkubo, H., Yoshida,A., Mayumi, M., Mikawa, H., Fundamental and clinical studies of cefuzonam in pediatrics,jpn j of antibiot,Vol.40(2)pg.385-395

Antibiotic name Diseases treated m log P Cefalexin (cephalexin) , strep throat =-1.486

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-7-{[(2R)-2-amino-2- 64mg/L, Bacteroides fragilis =O)[C@@H](c3ccccc3)N)C)C(=O)O phenylacetyl]amino}- 3-methyl- 8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene- 2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H17N3O4S, 347.39 g/mol First-generation cephalosporins Keflex, Keftab

Dipole Moment (Debye) Molecular Volume Surface Area 5.98 Debyes 327.46Å3 351.56Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 112.729Å2 15686-71-2 0.0183 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 7

References and summary a. MOA: Cephalexin inhibits the synthesis of the cell wall. [Russell, A., Fountain, R., Aspects of the mechanism of action of some cephalosporins, J.Bacteriol., 106(1), p. 65-69, 1971]

b. Source: Cephalexin was synthesized from cephalosporin C which was isolated from the fungus Cephalosporium acremonium. [Ryan, C., Simon, R., Heyningen, E., Chemistry of cephalosporin antibiotics. XIII. Deacteoxycephalosporins. Synthesis of cephalexin and some analogs, J. Med. Chem., 12(2), pp. 310-313, 1969]

c. Cell line Test (MIC): Cephalexin and other antibiotics have been tested on a variety of different microbes. All the minimum inhibitory concentrations are recorded. Against Escherichia coli strain NCTC 10418, Cephalexin had a minimum inhibitory concentration of 4mg/L. [Andrews, J., Determination of minimum inhibitory concentrations, Journal of Antimicrob. Chemother., 48(supplement 1), pp. 5-16, 2001]

d. Human clinical trials: In this study, cephalexin and trimethoprim-sulfamethoxazole were used to treat patients infected with community-associated methicillin-resistant Staphylococcus aureus at Brigham and Women’s Hospital. [Pallin,D., Binder, W., Allen, M., Lederman, M., Parmar, S., Filbin, M., Hooper, D., Camargo, C., Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated : a randomized controlled trial, Clin. Infect. Dis., 56(12), pp. 1754-1762, 2013]

e. Review Article: Cephalexin is an oral semi-synthetic antibiotic that has been used to treat many diseases such as impetigo. This article summarizes the other uses, antibacterial activity, and history of cephalexin. [ Speight, T., Brogden, R., Avery, G., Cephalexin: a review of its antibacterial, pharmacological and therapeutic properties, Drugs, 3(1-2), pp. 9-78, 1972]

Antibiotic name: Diseases treated: Typhoid, m log P= Chloramphenicol Salmonella typhi, Cholera 0.731

SMILES: IUPAC: MIC values: c1cc(ccc1[C@H]([C@@H](CO)NC(=O)C(Cl) 2,2-dichloro -N-[1,3-dihydroxy-1- Against Escherichio coli 0.015 µg/ml-

Cl)O)[N+](=O)[O-] (4-nitrophenyl)propan-2- 10,000 µg/ml, against Staphylococcus

yl]acetamide aureus 0.06 µg/ml->128 µg/ml and

against Streptococcus pneumonia 2

µg/ml-16 µg/ml

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C11H12Cl2N2O5, 323.132 g/mol Benzenoids Chloromycetin

Dipole Moment (Debye)= Molecular Volume= Surface Area= 8.06 Debye 249.156 Å3 296.05 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 115.378 Å2 56-75-7 0.0323 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N): atoms): 3 5

References and summary a. MOA: Chloramphenicol is a bacteriostatic drug that stops bacterial growth by inhibiting protein synthesis. Chloramphenicol prevents protein chain elongation by inhibiting the activity of the bacterial ribosome. It specifically binds to A2451 and A2452 residues in the 23S rRNA of the 50S ribosomal subunit, preventing peptide bond formation.( Jardetzky, Oleg. "Studies on the Mechanism of Action of Chloramphenicol I. THE CONFORMATION OF CHLORAMPHENICOL IN SOLUTION." Journal of Biological Chemistry 238.7 (1963): 2498- 2508.) b. Source: Chloramphenicol is derived from bacterium Streptomyces venezuelae. (Shapiro, S., and L. C. Vining. "Nitrogen metabolism and chloramphenicol production in Streptomyces venezuelae." Canadian journal of microbiology 29.12 (1983): 1706-1714.)

c. Cell line Test (MIC): Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery. The MIC value for CAP was 2.0 µg/ml. (Stevenson, M., A. J. Baillie, and R. M. Richards. "Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery." Antimicrobial agents and chemotherapy 24.5 (1983): 742-749.) d. Human clinical trials: In this clinical trial six strains of Actinomycies Israeli were inhibited by the concentration of chloromycetin ranging from 1-3 microgram per ml. (Littman, M. L., G. E. Phillips, and M. H. Fusillo. "In vitro susceptibility of human pathogenic actinomycetes to chloramphenicol (chloromycetin)." American journal of clinical pathology 20.11 (1950): 1076-1078.)

e. Review Article: Jardetzky, Oleg. "Studies on the Mechanism of Action of Chloramphenicol I. THE CONFORMATION OF CHLORAMPHENICOL IN SOLUTION." Journal of Biological Chemistry 238.7 (1963): 2498-2508. Shapiro, S., and L. C. Vining. "Nitrogen metabolism and chloramphenicol production in Streptomyces venezuelae." Canadian journal of microbiology 29.12 (1983): 1706-1714. Stevenson, M., A. J. Baillie, and R. M. Richards. "Enhanced activity of streptomycin and chloramphenicol against intracellular Escherichia coli in the J774 macrophage cell line mediated by liposome delivery." Antimicrobial agents and chemotherapy 24.5 (1983): 742-749. Littman, M. L., G. E. Phillips, and M. H. Fusillo. "In vitro susceptibility of human pathogenic actinomycetes to chloramphenicol (chloromycetin)." American journal of clinical pathology 20.11 (1950): 1076-1078. f.

Antibiotic name Diseases treated m log P Cilastatin Respiratory tract infection =-0.812

SMILES IUPAC MIC values N[C@@H](CSCCCC \C=C(/NC(=O)[C@H]1C (2Z)-7-{[(2R)-2-amino-2- 0.024-50µg for patients with C1(C)C)C(=O)O)C(=O)O carboxyethyl]sulfanyl}-2- Staphylococcus Aureus infections {[(1S)-2,2- dimethylcyclopropyl]formami

do}hept-2-enoic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H26N2O5S, Mass 358.459 g/mol Carbapenems Primaxin, Tienam and Zienam

Dipole Moment (Debye) Molecular Volume Surface Area 5.66 Debye 359.81 Å3 107.480Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 129.719Å2 82009-34-5 0.0157 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 11 available, attached to O, S, N) atoms) 5 7

References and summary a. MOA It’s mehcaniism of action is attacking the reversible renal dehydropeptidase-1 inhibitor. The drug is commonly used in a combination with Impenem.( Solomkin, JOSEPH S., et al. "Results of a multicenter trial comparing imipenem/cilastatin to tobramycin/clindamycin for intra-abdominal infections." Annals of surgery 212.5 (1990): 581.

b. Source It is derived from the compound which is produced by the bacterium Streptomyces cattley.( Kropp, Helmut, et al. "Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase-I." Antimicrobial agents and chemotherapy 22.1 (1982): 62-70.)

c. Cell line Test (MIC)The MIC value was between0.024-50µg for patients who suffered from methicillin sensitive and resistant Staphylococcus Aureus infections. (Fan, W., et al. "Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections." Antimicrobial agents and chemotherapy 29.1 (1986): 26-29.)

d. Human clinical trialsStudy Evaluating Tigecycline Versus Imipenem/Cilastatin in Hospital-Acquired Pneumonia . The trial was conducted to compare the efficacy and safety of the tigecycline regimen with a imipenem/cilastatin regimen in subjects who were infected with nosocomial pneumon. It had completed phase 3. i

e. Review ArticleResults of a Clinical Trial of Clinafloxacin Versus Imipenem/Cilastatin for Intraabdominal Infections (Solomkin, Joseph S., et al. "Results of a clinical trial of clinafloxacin versus imipenem/cilastatin for intra- abdominal infections." Annals of surgery 233.1 (2001): 79. The review article is about two drugs being tested to see what is more effective in treating infections with microorganism resistant bacteria.

Antibiotic nameCiprofloxacin Diseases treatedUrinary tract m log P infections -0.701

SMILES IUPAC1-cyclopropyl-6-fluoro-4- MIC values MIC 0.25-1.0 mg/L against c1c2c(cc(c1F)N3CCNCC3)n(cc(c2=O)C(=O) oxo-7-(piperazin-1-yl)-quinoline- decreased susceptibility to ciprofloxacin in Salmonella O)C4CC4 3-carboxylic acid

Emp. Formula, Molar mass Antibiotic groupFirst Generation Trade namesCipro

C17H18FN3O3, 331.346 g/mol Quinolones

Dipole Moment (Debye) 3.72 Debye Molecular Volume285.46 Å3 Surface Area424.235 Å2

Surface Area (TPSA) 74.569 Å2 CAS Number85721-33-1 D/V (dipoe moment/volume)0.013 Debye/ Å3

Rotatable # bonds3 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)2 atoms)6

References and summary a. MOA Inhibits DNA gyrase, a type II topoisomerase, enzyme necessary to separate bacterial DNA, therefore inhibiting cell division. (Brunton, L., et al. Mechanism of action and pharmakinetics of Ciprofloxacin. Goodman & Gilman's The Pharmacological Basis of Therapeutics. McGraw-Hill Prof Med/Tech)

b. Source Ciprofloxacin derives from Nalidixic acid (Emmerson, A., et al. The Quinolones: Decades of Development and Use. The Journal of Antimicrobial Chemotherapy. 51 (1); p. 13–20, 2002.

c. Cell line Test (MIC) ) In 1999, 23% of Salmonella enterica serotype Typhi isolates from patients in the United Kingdom exhibited decreased susceptibility to ciprofloxacin (MIC 0.25-1.0 mg/L). (Threlfall, E., Ward, L. Decreased susceptibility to ciprofloxacin in Salmonella enterica serotype typhi, United Kingdom. Emergency Infect Disease. 7(3); p. 448–450, 2001)

d. Human clinical trials In this trial ciprofloxacin was compared to mesalazine for the treatment of Crohn’s disease. (Duclos, B., et al. A controlled trial comparing ciprofloxacin with mesalazine for the treatment of active Crohn's disease. American Journal of Gastroenterology 94, 674–678, 1999)

e. Review Article Mégraud, F., Lamouliatte H., Helicobacter pylori and duodenal ulcer. Evidence suggesting causation. Dig Dis Sci. 37 (1); p. 769–72,1992)

Antibiotic name Diseases treatedpharyngitis, tonsillitis, m log P Clarithromycin acute maxillary sinusitis, pneumonia = 2.897

SMILES IUPAC MIC values O=C3O[C@H](CC)[C@](O)(C)[C@H](O)[C (3R,4S,5S,6R,7R,9R,11S,12R,13S,14S)-6- 1)0.25 µg/ml for isolates of @H](C(=O)[C@H](C)C[C@](OC)(C)[C@H]( {[(2S,3R,4S,6R) -4-(dimethylamino)-3- Mycobacterium chelonae subsp. hydroxy-6-methyloxan-2-yl]oxy} -14- O[C@@H]1O[C@H](C)C[C@H](N(C)C)[C@ ethyl-12,13-dihydroxy-4-{[(2R,4S,5S,6S)- Chelonae H]1O)C([C@H](O[C@@H]2O[C@H]([C@H 5-hydroxy -4-methoxy-4,6- 2)0.5 µg/ml for M. chelonae subsp. ](O)[C@](OC)(C2)C)C)[C@H]3C)C)C dimethyloxan-2-yl]oxy}-7 -methoxy- Abscessus 3,5,7,9,11,13-hexamethyl -1- oxacyclotetradecane-2,10-dione

Emp. Formula, Molar mass Antibiotic group Trade names C38H69NO13, 747.953 g/mol Macrolide Antibiotic, Macrolide Biaxin Antimicrobial

Dipole Moment (Debye) Molecular Volume Surface Area 5.85 Debye 341.84 Å3 354.14 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 71.391 Å2 81103-11-9 0.0171

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 14

References and summary a. MOA clarithromycin is effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures(Piscitelli S.C., Danziger L.H., Rodvold K.A., Clarithromycin and azithromycin: new macrolide antibiotics,Vol. 11(2),pg.137-152,1992

b. Source semisynthetic antibacterial (bhat,S.V.,Nagasampagi,B.A.,Sivakumar,M.,Chemistry of Natural Products,Narosa publishing house,pg.722,2005

c. Cell line Test (MIC) clarithromycin for 90% of strains tested (MIC90) was 0.25 µg/ml for isolates of Mycobacterium chelonae subsp. chelonae and 0.5 µg/ml for M. chelonae subsp. abscessus, with 100% of strains inhibited by less than or equal to 1 µg/ml.(Brown, B.A.,Wallace,R.J.,Rosas V.D.,Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms, Antimicrob. Agents Chemothervol.,Vol. 36(1),pg. 180-184. January 1992)

d. Human clinical trials 3768 patients were receiving clarithromycin in phase II and III trials were nausea (3.8%), diarrhoea (3.0%), abdominal pain (1.9%) and headache (1.7%).(David R. P., Guay, D,. Patterson R., Seipman N., Craft J.C., Overview of the Tolerability Profile of Clarithromycin in Preclinical and Clinical Trials, Vol. 8(5),pg. 350-364,Nay 1993.

e. Review Article 1. Kelley M. A.,Weber D. J.,Gilligan P.,Myron S. C., Breakthrough Pneumococcal Bacteremia in Patients Being Treated with Azithromycin and Clarithromycin,Clin. Infect. Dis., Vol.31(4)pg. 1008-1011,2000. 2. Whitman M.S., Tunkel A.R., Azithromycin and clarithromycin: overview and comparison with erythromycin, Infect Control Hosp Epidemiol.,Vol.13(6)pg.357-68. June1992

Antibiotic name Diseases treated m log P Clinafloxacin Bacterial Endocarditis =-.396

SMILES IUPAC MIC values Fc2c(c(Cl)c1N(/C=C(/C(=O)O)C(=O)c1c2)C 7-(3-Aminopyrrolidin-1-yl)-8- 0.06 µg/mL, Streptococcus pneumoniae 3CC3)N4CCC(N)C4 chloro-1-cyclopropyl-6-fluoro-4- oxoquinoline-3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C17H17ClFN3O3, 365.786 g/mol Fluoroquinolone ( Fourth- Vetranal generation quinolones)

Dipole Moment (Debye) Molecular Volume Surface Area 6.16 Debyes 331.30 Å3 345.10 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 88.565 Å2 105956-97-6 0.0178 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA: Clinafloxacin inhibits DNA synthesis. [Hooper, D., Mechanisms of action of antimicrobials: focus on fluroroquinolone, Clin. Inf. Dis., 32 (supplement 1), pp. S9-S15, 2001]

b. Source: Clinafloxacin is a synthetic antibiotic. [Randinitis, E., Koup, J., Rausch, G., Abel,R., Bron, N., Hounslow, N., Vassos, A., Sedman, A., Clinafloxacin pharmacokinetics in subjects with various degrees of renal functions, Antimicrobiol. Ag. Chemother., 45(9), pp. 2536-2542, 2001]

c. Cell line Test (MIC): Clinafloxacin ‘s inhibitory concentration iwere determined with different bacterium. For Streptococcus pneumoniae, the concentration at which this bacterium is 0.06 µg/mL. [Levine, D., Holley, P., Eiseman, I., Wilcox, P., Tack, K., Clinafloxacin for the treatment of bacterial endocarditis, Clin. Inf. Dis., 38(5), pp. 620-631, 2004]

d. Human clinical trials: In this trial, clinafloxacin is used to treat patients who are granulocytopenic. This study was conducted in numerous hospitals such as Case Western University Hospital, Fairfax Hospital, and Vancouver Hospital.[Winston, D., Lazarus, H., Berveridge, R., Hathorn, J., Gucalp, R., Ramphal, R., Chow, A., Ho, W., Horn, R., Feld, R., Louie, T., Territo, M., Blumer, J., Tack, K., Randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients, Clin. Inf. Dis., 32(3), pp. 381-390, 2001]

e. Review Article: In this study, clinafloxacin’s pharmacological properties were summarized. [Stein, G., Pharmacokinetics and pharmacodynamics of newer fluoroquinolones, Clin. Inf. Dis., 23 (supplement 1), pp. S19- S24, 1996]

Antibiotic nameClindamycin Diseases treated Protozoal m log P diseases 2.064

SMILES IUPAC methyl 7-chloro-6,7,8- MIC values0.4-0.6 mg/ml for Cl[C@@H](C)[C@@H](NC(=O)[C@H]1N(C trideoxy-6-{[(4R)-1-methyl-4- clindamycin against Staphylococcus )C[C@H](CCC)C1)[C@H]2O[C@H](SC)[C@ propyl-L-prolyl]amino}-1-thio-L- H](O)[C@@H](O)[C@H]2O threo-α-D-galacto- octopyranoside

Emp. Formula, Molar mass Antibiotic groupLincosamides Trade namesDalacin C18H33ClN2O5S, 424.98 g/mol

Dipole Moment (Debye)4.17 Debye Molecular Volume384.724 Å3 Surface Area414.850 Å2

Surface Area (TPSA) 102.254 Å2 CAS Number18323-44-9 D/V (dipoe moment/volume)0.011 Debye/ Å3

Rotatable # bonds7 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)4 atoms)7

References and summary a. MOA Clidamycin is a protein synthesis inhibitor by inhibiting ribosomal translocation, similar to macrolides. It binds to the 50S RNA of the large bacterial ribosome subunit. (Darley, E., et al. Antibiotic treatment of gram- positive bone and joint infections. J. Antimicrobial Chemotherapy. 53 (6); p. 928–935, 2004)

b. Source Clindamycin derives from actinobacterium Streotomyces lincolnensis. (Jain, G., et al. Adapalene pretreatment increases follicular penetration of clindamycin: in vitro and in vivo studies. Indian J Dermatol Venereol Leprol. 73 (5); p. 326–329, 2007)

c. Cell line Test (MIC) MIC =0.4-0.6 mg/ml for clindamycin against Staphylococcus. (Daum, R., Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. N Engl J Med. 357 (4); p. 380–390, 2007)

d. Human clinical trials Trial A was carried out to determine the treatment of infection due to Pneumocystis carinii. (Fishman, J.A. Treatment of Infection Due to Pneumocystis carini. Antimicrobial Agents and Chemotherapy. 42 (6); p. 1309–1314, 2008. .

e. Review Article Lell B, Kremsner P.G. Clindamycin as an Antimalarial Drug: Review of Clinical Trials. Antimicrobial Agents and Chemotherapy 46 (8); p. 2315–20, 2002)

Antibiotic name Diseases treated m log P Clofazimine Leprosy = 8.431

SMILES IUPAC MIC values Clc1ccc(cc1)NC=3/C(=N/C(C)C)/C= N,5-bis(4-chlorophenyl)-3- 3 μg/ml when used against M.

C2/N(c4c(\N=C2C=3)cccc4)c5ccc(Cl) (propan-2-ylimino)-3,5- intracellulare cc5 dihydrophenazin-2-amine

Emp. Formula, Molar mass Antibiotic group Trade names C27H22Cl2N4, 473.407 g/mol Riminophenazine Lamprene

Dipole Moment (Debye) Molecular Volume Surface Area 5.12 Debye 464.93 Å3 476.62 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 24.782 Å2 2030-63-9 0.011 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 1 4

References and summary a. MOA Clofazimine binds to the guanine bases of DNA enabling the bacterium to grow. (Kaneko, T., et al., Challenges and opportunities in developing novel drugs for TB, Future Medicinal Chemistry, Vol. 3, No. 11, p. 1373-1400, 2011)

b. Source The synthesis of riminophenazines gave rise to Clofazimine. (Zhang, G., et al., Synthesis of New Riminophenazines with Pyrimidine and Pyrazine Substitution at the 2-N Position, Molecules, Vol. 16, p. 6985-6991, 2011)

c. Cell line Test (MIC) Multiple drugs were used to determine their MIC values against different Mycobacteria. (Gomez-Flores, R., et al., Determination of MICs for Mycobacterium avium-M. intracellulare complex in liquid medium by a colorimetric method, Journal of Clinical Microbiology,Vol. 33, No. 7, p. 1842-1846, 1995)

d. Human clinical trials Clinical trial testing the potency of Clofazimine in treating lepromatous leprosy. (Ji, B., et al., Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy, Antimicrobial Agents and Chemotherapy, Vol. 38 No. 4, p. 662-667, 1994)

e. Review Article A review pertaining to the usefulness of Clofazimine in treating tuberculosis. (Gopal, M., et al., Systematic review of clofazimine for the treatment of drug-resistant tuberculosis [Review article], The International Journal of Tuberculosis and Lung Disease, Vol. 17, No. 8, p. 1001-1007, 2013)

Antibiotic name Diseases treated m log P Cloxacillin Bacterial Meningitis =2.662

SMILES IUPAC MIC values O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O (2S,5R,6R)-6-{[3-(2- 64 mg/L, Methicillin-Resistant )c2c(onc2c1ccccc1Cl)C)[C@H]4SC3(C)C chlorophenyl)-5-methyl- Staphyloccocus aureus oxazole-4-carbonyl]amino}-3,3- dimethyl-7-oxo- 4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid Emp. Formula, Molar massC19H18ClN3O5S, Antibiotic group Trade names 435.88 g/mol Pencillins Cloxapen, Cloxacap, Tegopen, Orbenin

Dipole Moment (Debye) Molecular Volume Surface Area 1.83 Debyes 389.43 Å3 411.50 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 112.738 Å2 61-72-3 0.00470 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 2 8

References and summary a. MOA: Cloxacillin inhibits cell wall synthesis. [Arkbarzadeh, T., Fallah, T., Samadi, N., Foroumadi, A., Amanlou, M., Faramarzi, M., Shafiee, A., Synthesis and cloxacillin antimicrobial enhancement of 2-methylsufonyllimidazolyl-1,4- dihydropyridine derivatives, DARU, 18(2), pp. 118-123, 2010].

b. Source: Cloxacin is a semisynthetic antibiotic from the original penicillin extracted from the fungus in the genus, Penicillum. . [Arkbarzadeh, T., Fallah, T., Samadi, N., Foroumadi, A., Amanlou, M., Faramarzi, M., Shafiee, A., Synthesis and cloxacillin antimicrobial enhancement of 2-methylsufonyllimidazolyl-1,4-dihydropyridine derivatives, DARU, 18(2), pp. 118-123, 2010].

c. Cell line Test (MIC): In this study, Cloxacillin inhibited the growth of Methicillin-Resistant Staphylococcus aureus at a minimum concentration of 64 mg/L. [Somekh, E., Golan, T., Tanay, A., Poch, F., Dan, M., Concentration and bactericidal activity of fusidic acid and cloxacillin in serum and synovial fluid, J. Antimicrob. Chemother., 43, pp. 593-596, 1999].

d. Human clinical trials: Cloxacillin was used to treat patients with Chediak-Higashi syndrome at the National Institute of Health Clinical Center. [Dale, D., Alling, D., Wolff, S., Cloxacillin chemoprophylaxis in the Chediak-Higashi Syndrome, J. Infect. Dis., 125(4), pp. 393-397, 1072].

e. Review Article: In this study, the uses of Cloxacillin for various infections are discussed. [Ki, V., Rotstein, C., Bacterial skin and soft tissue infections in adults: a review of their epidemiology, pathogenesis, diagnosis, treatment and site of care, Can. J. Infect. Dis. Med. Microbiol., 19(2), pp. 173-184, 2008].

Antibiotic name Diseases treated m log P Cycloserine Tuberculosis, Gaucher's disease = -1.898

SMILES IUPAC MIC values O=C1NOC[C@H]1N (R)-4-Amino-1,2-oxazolidin-3- 1. Cycloserine was investigated 15 one methicillin-susceptible Staphylococcus aureus strains with 0 25 µg/ml. 1

⋅

Emp. Formula, Molar mass Antibiotic group Trade names C3H6N2O2, 102.092 g/mol streptomyces derivatives Seromycin

Dipole Moment (Debye) Molecular Volume Surface Area 2.68 Debye 93.71 Å3 118.65 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 65.966 Å2 68-41-7 0.028 Debtye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 0 available, attached to O, S, N) atoms) 3 4

References and summary a. MOA D-cycloserine inhibits the formation of the cell membrane more strongly than protein synthesis, whereas L- cycloserine inhibits both processes equally(Vyshepan E.D., Ivanova K.I.,Lendeva R.K., The mechanism of the action of stereoisomers of cycloserine on bacterial cells,Exp. Biol. Medic.,Vol.52(4),pg. 1159-1161,May 1962.

b. Source Cycloserine produced by a strain of Streptomyces orchidaceus and has also been synthesized.(Hidy P.H.,Hodge E.B.,(Hidy P.H.,Hodge E.B.,oung V.V.,Harned R.L.,Glenn A.B.,Phillips W.F.,Runge W.F.,Stavely H.E.,Pohland A.,Boaz H.,Sullivan H.R., Structure and reactions of cycloserine, J. Am. Chem. Soc.,Vol.77(8),pg. 2345-2346,April 1995.

c. Cell line Test (MIC) Cycloserine was investigated 15 methicillin-susceptible Staphylococcus aureus strains with 0 25 µg/ml(Komatsuzawa. H.,Suzuki J.,Sugai M.,Miyake Y.,Suginaka H., Effect of combination of oxacillin and non-β- lactam antibiotics on methicillin-resistant Staphylococcus aureus, J. Antimicrob. Chemother.,Vol.⋅ 33(6),pg. 155- 1163. d. Human clinical trials 31 patients were given 50 mg dose of d-cycloserine in a double-blind, placebo-controlled augmentation trial examining.(Otto M.W.,Tolin D.F.,Simon N.M.,Pearlson G.D.,Badsen S.,Meunier S.A.,Hofmann S.G.,Eisenmenger K.,Krystal J.H.,Pollack M.H., Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder,Biol. Psych.,Vol.67(4),pg. 365-370, 15 February 2010.

e. Review Article 1. Komatsuzawa. H.,Suzuki J.,Sugai M.,Miyake Y.,Suginaka H., Effect of combination of oxacillin and non-β-lactam antibiotics on methicillin-resistant Staphylococcus aureus, J. Antimicrob. Chemother.,Vol.33(6),pg. 155-1163. 2.Kushner M.G.,Kim S.K.,Donahue C.,Thuras P.,Adson D., Kotlyar M., McCabe J., Peterson J., Foa E.B., D- Cycloserine Augmented Exposure Therapy for Obsessive-Compulsive Disorder,Biol. Psy.,Vol.62(8),pg. 835- 838,October 2007.

Antibiotic name Diseases treated m log P Dapsone Dermatitis herpetiformis = 0.932

SMILES IUPAC MIC values C1=CC(=CC=C1N)S(=O)(=O)C2=CC 4-[(4- At a concentration of 8 mg/L, =C(C=C2)N aminobenzene)sulfonyl]anilin dapsone inhibits the growth of e M. avium.

Emp. Formula, Molar mass Antibiotic group Trade names C12H12N2O2S Sulfone Aczone 248.302 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 7.06 Debye 238.16 Å3 263.75Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 83.053 Å2 80-08-0 0.0296 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 4

References and summary a. MOA Dapsone works by inhibiting folic acid synthesis in susceptible microorganisms. (Voeller D, Kovacs J, Andrawis V, et al. Interaction of Pneumocystis carinii dihydropteroate synthase with sulfonamides and diaminodiphenylsulfone (dapsone). J. Infect. Dis., 169, 456-459, 1994.)

b. Source Dapsone was manufactured synthetically from para-chloronitrobenzene. (Windholz M, ed. The Merck index. 9th ed. Rahway, NJ: Merck and Co, 370, 1976.)

c. Cell line Test (MIC) At a concentration of 8 mg/L, dapsone inhibits the growth of M. avium, M. intracellulare, M. kansasii, and M. fortuitum. (Gonzalez, A. H., Berlin, O. G. W., Bruckner, D. A., In-vitro activity of dapsone and two potentiators against Mycobacterium avium complex., J. Antimicrob. Chemother., 24 (1), 19-22, 1989.) d. Human clinical trials 18 patients suffering from PCP were given 100 mg of dapsone daily for 21 days. 60% of the patients condition improved within 3-10 days. (Mills, J., Leoung, G., Medina, I., et al., Dapsone treatment of Pneumocystis carinii pneumonia in the acquiredimmunodeficiency syndrome. Antimicrob. Agents Chemother., 1057-1060, 1988.)

e. Review Article [1]. Hughes, W. T., Use of Dapsone in the Prevention and Treatment of Pneumocystis carinii Pneumonia: A Review., Clin. Inf. Dis., 27, 191-204, 1998. [2]. Zhu, Y. I., Stiller, M. J., Dapsone and sulfones in dermatology: Overview and update., J. Amer. Acad. Dermatol. 45(3), 420-434. 2001.

Antibiotic name Diseases treated active against m log P Daptomycin gram positive pathogens = -4.688

SMILES IUPAC MIC values CCCCCCCCCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C( N-decanoyl-L-tryptophyl-L- 0.125 to 0.25 mg/L of daptomycin is =O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(= asparaginyl-L-aspartyl-L- active against ATCC 25923 strain of O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)c2ccc threonylglycyl- MSSA at the pH of 7.4 cc2N)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O) L-ornithyl-L-aspartyl-D-alanyl-L-

CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O) aspartylglycyl-D-seryl-threo -3- [C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1 =O)[C@H](C)CC(O)=O methyl-L-glutamyl-3-anthraniloyl- L-alanine[egr]1-lactone

Emp. Formula, Molar mass Antibiotic group Trade names C72H101N17O26 Cyclic lipopeptides Cubicin 1619.7086 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area Debye 1435.27 Å3 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 702.005 Å2 103060-53-3 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 38 available, attached to O, S, N) atoms) 25 43

References and summary a. MOA Association of Ca2+ with daptomycin interefere with the bacterial membrane (Jung, D. et al., Structural Transitions as Determinants of the Action of the Calcium-Dependent Antibiotic Daptomycin ., Chem. & Biol. 11, 949-957, 2004.)

b. Source Daptomycin was isolated from the Streptomyces roseosporus. (Tally, F. P. and DeBruin, M. F. Development of daptomycin for Gram-positive infections, J. Antimicrob. Chemother., 46, 523-526, 2000.)

c. Cell line Test (MIC) 0.125 to 0.25 mg/L of daptomycin is active against ATCC 25923 strain of MSSA at the pH of 7.4 (Aurelie M. et al., Activity of ceftaroline against extracellular (broth) and intracellular (THP-1 monocytes) forms of methicillin-resistant Staphylococcus aureus: comparison with vancomycin, linezolid and daptomycin. J. Antimicrob. Chemother. 68, 648-658, 2013.) d. Human clinical trials 133 patients were enrolled in a randomized study to assess the effectiveness of daptomycin against penicillins or vancomycin in treating infected diabetic foot ulcer. (Lipsky, A., et al. Daptomycin for treating infected diabetic foot ulcers: evidence from a randomized, controlled trial comparing daptomycin with vancomycin or semi-synthetic penicillins for complicated skin and skin-structure infections. J. Antimicrob. Chemother. (55)2, 240-245, 2005.) e. Review Article [1]. Arbeit, R. D., Maki, D., Tally, F. P., Campanaro, E., Eisenstein, B. I., The Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin-Structure Infections. Clin. Infect. Dis. 38(12), 1673-1681, 2004. [2]. Falagas, M. E., Giannopoulou, K. P., Ntziora, F., Vardakas, K. Z., Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence, J. Antimicrob. Chemother. 60(1), 7-19, 2007.

Antibiotic name Diseases treated pneumonia, m log P -0.643 Demeclocycline acne, other bacterial infections

SMILESCN(C)[C@H]1[C@@H]2C[C@@H] IUPAC (2E,4S,4aS,5aS,6S,12aS)- MIC values 3[C@@H](C4=C(C=CC(=C4C(=O)C3=C([C 2-[amino(hydroxy)methylidene]- 2.0 µg/mL; Staphylococci, Streptococci, @@]2(C(=O)C(=C1O)C(=O)N)O)O)O)Cl)O 7-chloro-4-(dimethylamino)- M. Cartarrhalis, and H. Influenzae 6,10,11,12a-tetrahydroxy- 1,2,3,4,4a,5,5a,6,12,12a- decahydrotetracene-1,3,12- trione

Emp. Formula, Molar mass Antibiotic group Trade names C21H21ClN2O8, 464.853 g/mol Tetracycline Declomycin®

Dipole Moment (Debye) Molecular Volume Surface Area 4.12 Debye 399.32 Å3 401.72 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 181.614 Å2 127-33-3 0.0103 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 7 10

References and summary a. MOA Demeclocycline is a bacterostatic antibiotic that affects susceptible bacteria by binding to 30S and possibly the 50S ribosomal subunits to disrupt protein synthesis. (Koza, Darrell J. Synthesis of 7-Substituted Tetracycline Derivatives. Organic Letters. Vol 2, No. 6, 2000.)

b. Source Demeclocyline is a semi-synthetic antibiotic, in the tetracycline family. Tetracycline was first derived from Streptomyces aurefaciens, Demeclocycline is a 7-substituted analogue of this primary structure. (Koza, Darrell J. Synthesis of 7-Substituted Tetracycline Derivatives. Organic Letters. Vol 2, No. 6, 2000.)

c. Cell line Test (MIC) Staphylococci, Streptococci, M. Cartarrhalis, and H. Influenzae; 2.0 µg/mL. (MacGowan, A.P., Richard wise. Establishing MIC breakpoints and the Interpretations on In-vitro Susceptibility Tests. Journal of Anitmicrobial Chemotherapy. 48, 17-28, 2001.)

d. Human clinical A clinical trial was conducted to access the degree of short term post-operative irritation after application of a triamcinolone/demeclocycyline based or a calcium hydroxide based provisional cement trials (A prospective clinical trial on the influence of a triamcinolone/demeclocycline and a calcium hydroxide based temporary cement on pain perception. Head & Face Medicine. 8(1), 9-14, 2012.)

e. Review Article Carrilho F, Bosch J, Arroyo V, Mas A, Viver J, Rodes J. Renal failure associated with demeclocycline in cirrhosis. Annals Of Internal Medicine. 87(2), 195-197, 1977.

Antibiotic name Diseases treated: Pneumonia, m log P Dicloxacillin urinary tract infections = 3.292

SMILES IUPAC MIC values O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O (2S,5R,6R)-6-{[3-(2,6- Staphylococci aureus 1 mg/L )c2c(onc2c1c(Cl)cccc1Cl)C)[C@H]4SC3(C) dichlorophenyl)-5-methyl- C oxazole-4-carbonyl]amino}-3,3- dimethyl-7-oxo-4-thia- 1-azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C19H17Cl2N3O5S , 470.327 g/mol Penicillins Dynapen, Dycill, Pathocil

Dipole Moment (Debye) Molecular Volume Surface Area 3.80 Debye 403.52 Å3 431.26 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 96.908 Å2 3116-76-5 0.009 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 2 11

References and summary a. MOA: Dicloxacillin inhibits bacterial cell wall synthesis. (Fisher, J. F.; Meroueh, S. O.; Mobashery, S. (2005). "Bacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity†". Chemical Reviews 105 (2): 395–424)

b. Source: N/A

c. Cell line Test (MIC): Dicloxacillin was tested against various S. aureus strains in peritoneal fluid and in the kidneys of mice with different phenotypes. Treatment with dicloxacillin was determined to be effective . Mice with phenotype WT (wild-type) had a MIC against S. aureus found to be 0.25 mg/L while those with phenotype SCV (small-colony- variant) had a MIC of 0.06 mg/L. (Sandberg, Anne, et al. "Intra- And Extracellular Activities Of Dicloxacillin And Linezolid Against A Clinical Staphylococcus Aureus Strain With A Small-Colony-Variant Phenotype In An In Vitro Model Of THP-1 Macrophages And An In Vivo Mouse Peritonitis Model." Antimicrobial Agents And Chemotherapy 55.4 (n.d.): 1443-1452) d. Human clinical trials: Dicloxacillin is used to treat patients with infected central indwelling catheters. (Pfizer, Inc. ClinicalTrials.gov Identifier: NCT00037050. Sept 2009.)

e. Review Article: N/A

Antibiotic name Diseases treated Respiratory m log P Dirithromycin infections caused by Legionella, = 3.116

SMILES O=C4O[C@@H]([C@](O)(C)[C IUPAC MIC values @H]1O[C@@H](N[C@H]([C@@H]1 (2R,3R,6R,7S,8S,9R,10R,12R,13S,15R,17S 1-4 µg/ml of Dirithromycin was )-9-{[(2S,3R,4S,6R)-4-(dimethylamino)-3- C)[C@H](C)C[C@](O)(C)[C@H](O[C hydroxy-6-methyloxan-2-yl]oxy}-3-ethyl- shown to be senstive against @@H]2O[C@H](C)C[C@H](N(C)C)[ 2,10-dihydroxy-7-{[(2R,4R,5S,6S)-5- U. urealyticum C@H]2O)[C@H]([C@H](O[C@@H]3 hydroxy-4-methoxy-4,6-dimethyloxan-2- yl]oxy}-15-[(2-methoxyethoxy)methyl]- O[C@@H](C)[C@H](O)[C@@](OC)( 2,6,8,10,12,17-hexamethyl-4,16-dioxa-14- C)C3)[C@H]4C)C)COCCOC)CC azabicyclo[11.3.1]heptadecan-5-one

Emp. Formula, Molar mass Antibiotic group Trade names C42H78N2O14 Macrolide Dynabac 835.086 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 4.22 Debye 863.32 Å3 851.22 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 137.360 Å2 62013-04-1 0.0049 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 12 available, attached to O, S, N) atoms) 5 16

References and summary a. MOA Dirithromycin targets bacteria by inhibiting protein synthesis by binding to 23S ribosomal RNA found in the large ribosomal subunit (50S subunit) (Jain, R., Danziger, L. H., The Macrolide Antibiotics: A Pharmacokinetic and Pharmacodynamic Overview, Curr. Pharm. Des., 10(25), 3045-3053, 2004.)

b. Source Dirithromycin is a semisynthetic drug derived from erythromycin, which was originally isolated from Streptomyces erythreus (Jain, R., Danziger, L. H., The Macrolide Antibiotics: A Pharmacokinetic and Pharmacodynamic Overview, Curr. Pharm. Des., 10(25), 3045-3053, 2004.)

c. Cell line Test (MIC) 1-4 µg/ml of Dirithromycin was shown to be senstive against U. urealyticum (Kenny, G. E., Cartwright, F. D., Susceptibilities of Mycoplasma hominis, M. pneumoniae, and Ureaplasma urealyticum to GAR-936, Dalfopristin, Dirithromycin, Evernimicin, Gatifloxacin, Linezolid, Moxifloxacin, Quinupristin-Dalfopristin, and Telithromycin Compared to Their Susceptibilities to Reference Macrolides, Tetracyclines, and Quinolones, Antimicro. Agents Chemother. 45(9), 2604-2608, 2001.) d. Human clinical trials 591 patients enrolled in a double-blind study that tested the efficacy of dirithromycin in treating community-acquired bacterial pneumonia. Researchers concluded that 500 mg of dirithromycin once daily, was safe and effective in the treatment of ACP. (Liippo, K., Tala, E., Puolijoki, H., Brückner, O. -J., Rodrig, J., Smits, J. P. H., A comparative study of dirithromycin and erythromycin in bacterial pneumonia, J. Inf., 28(2), 131-139, 1994.) e. Review Article [1]. Zhanel, G. G., Dueck, M., 2 Hoban, D. J., Vercaigne, L. M., Embil, J. M., Gin, A. S., Karlowsky, J. A., Review of Macrolides and : Focus on Respiratory Tract Infections, Drugs, 61(4), 443-493, 2001. [2]. McConnell, S. A., Amsden, G. W., Review and Comparison of Advanced-Generation Macrolides Clarithromycin and Dirithromycin, Pharmacotherapy, 19(4), 404-415, 1999.

Antibiotic name Diseases treatedused for m log P doripenem abdominal infections, kidney inf. = -1.215

SMILES IUPAC MIC values O=S(=O)(N)NC[C@H]3NC[C@@H](S\ (4R,5S,6S)-6-(1-hydroxyethyl)-4- 2-8 μg/mL against Pseudomonas 1 C2=C( \N1C(=O)[C@H]([C@H](O)C)[C methyl-7-oxo-3-[(3S,5S)- aeruginosa isolates @H]1[C@H]2C)C(=O)O)C3 5[(sulfamoylamino)methyl]pyrro lidin-3-yl]sulfanyl-1- azabicyclo[3.2.0]hept-2-ene-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C15H24N4O6S2, 420.504 g/mol carbapenems finibex doribex

Dipole Moment (Debye) Molecular Volume Surface Area 4.60 Debye 375.94 Å3 418.74 Å3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 160.176 Å2 148016-81-3 0.0122 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 10 6

References and summary a. MOA Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Grampositivepathogens.(Poulakou,G.,Giamarrelou, H., Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens, Expert Opinion on Investigational Drugs, Vol.17(5), Pg.749-771, May 2008.,

b. Source Beta-lactam Derivative(El-Gamal, Mohammed, Chang-Hyun, Current Status of Carbapenem Antibiotics,Curr. Topics in Med. Chem., Vol. 10(18),pg.1882-1897,December 2010.

c. Cell line Test (MIC) 2-8 μg/mL against Pseudomonas aeruginosa isolates.( . Holly K. H., Douglas J. B., Ronald N. J., Delayed resistance selection for doripenem when passaging Pseudomonas aeruginosa isolates with doripenem plus an aminoglycoside, Diag micro and inf desease,Vol. 55(3),pg. 241-243,July 2006.

d. Human clinical trials 476 patients enrolled in trial of patients with cIAI.( Christopher L.,Jasovich A., Umeh O., Jiang J., Kaniga K., Friedland I., Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra- abdominal infection: A phase III, prospective, multicenter, randomized, double-blind, noninferiority study,clin therap,Vol.30(5),pg.868-883,may 2008.

e. Review Article 1. Holly K. H., Douglas J. B., Ronald N. J., Delayed resistance selection for doripenem when passaging Pseudomonas aeruginosa isolates with doripenem plus an aminoglycoside, Diag micro and inf desease,Vol. 55(3),pg. 241-243,July 2006 2.Jones,R.N.,Huynh,H.K.,Biedenbach,D.J.,Fristche,T.R.,Sader H.S., Doripenem (S-4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluations,J. Antimicrob Chemother.,Vol.54(1), Pg. 144-154

Antibiotic name Diseases treated m log P Doxorubicin Cancer = 0.567

SMILES IUPAC MIC values

C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C (7S,9S)-7-[(2R,4S,5S,6S)-4- 0.025 μg/ml and 0.25–2.5 μg/ml when

@H]2C[C@@](Cc3c2c(c4c(c3O)C(=O)c5cc amino-5-hydroxy-6-methyloxan- tested for inhibition against cc(c5C4=O)OC)O)(C(=O)CO)O)N)O 2-yl]oxy-6,9,11-trihydroxy-9-(2- Streptococcus mutans and Streptococcus

hydroxyacetyl)-4-methoxy-8,10- sanguis

dihydro-7H-tetracene-5,12-

dione

Emp. Formula, Molar mass Antibiotic group Trade names C27H29NO11 , 543.52 g/mol Anthracycline Adriamycin

Dipole Moment (Debye) Molecular Volume Surface Area 5.20 Debye 506.81 Åᶾ 154.28 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 206.078 Ų 23214-92-8 0.0103 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 6 12

References and summary a. MOA Doxorubicin inhibits the replication process. (Jackson, Trachette L. "Intracellular accumulation and mechanism of action of doxorubicin in a spatio-temporal tumor model." Journal of theoretical Biology 220.2 (2003): 201-213.

b. Source The natural source of Doxorubicin was found to be Streptomyces peucetius. (Guilfoile, Patrick G., and C. Richard Hutchinson. "A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin." Proceedings of the National Academy of Sciences 88.19 (1991): 8553-8557.

c. Cell line Test (MIC) A cell line test of 0.025 μg/ml and 0.25–2.5 μg/ml was carried out to test for inhibition against Streptococcus mutans and Streptococcus sanguis.( Meurman, Jukka H., Heini Torkko, and Seppo Pyrhönen. "Antineoplastic agents inhibit the growth of Streptococcus mutans and Streptococcus sanguis in vitro." Oral microbiology and immunology 6.3 (1991): 177-181. d. Human clinical trials A human clinical trial was carried out to determine the efficacy of Doxorubicin in women with breast cancer. (Lankelma, Jan, et al. "Doxorubicin gradients in human breast cancer." Clinical Cancer Research 5.7 (1999): 1703- 1707.

e. Review Article A combination of Docetaxel/Doxorubicin when treated for metastatic breast cancer. (Dieras, V. "Review of docetaxel/doxorubicin combination in metastatic breast cancer." Oncology (Williston Park, NY) 11.8 Suppl 8 (1997): 31-33.

A review of doxorubicin and how it treats patients with Primary lymphoma of the prostate. (Sarris, Andreas, et al. "Primary lymphoma of the prostate: good outcome with doxorubicin-based combination chemotherapy." The Journal of urology 153.6 (1995): 1852-1854.

Antibiotic name Diseases treated m log P Doxycycline Lyme Disease, Sinusitis =-0.873

SMILES IUPAC MIC values O.CN(C)[C@@H]3C(\O)=C(\C(N)=O)C(=O)[ (4S,4aR,5S,5aR,6R,12aS)-4- 1-8 µg/mL, Coxiella burnetti C@@]4(O)C(/O)=C2/C(=O)c1c(cccc1O)[C (dimethylamino)- 3,5,10,12,12a- @H](C)[C@H]2[C@H](O)[C@@H]34 pentahydroxy- 6-methyl- 1,11- dioxo- 1,4,4a,5,5a,6,11,12a- octahydrotetracene- 2- carboxamide

Emp. Formula, Molar mass Antibiotic group Trade names C22H24N2O8, 444.44 g/mol Macrolide Antibiotics Doryx, Vibramycin, Monodox, Microdox, Periostat, Vibra-Tabs, Oracea, Vibrox, Adoxa, Doxyhexal, Doxylin, Doxoral, Doxy-1, and Atridox

Dipole Moment (Debye) Molecular Volume Surface Area 7.13 Debyes 405.26 Å3 399.28 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 181.614 Å2 564-25-0 0.0176 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 7 10

References and summary a. MOA: Doxycycline inhibits MMP (Protein) synthesis. [[Krakauer, T., Buckley, M., Doxycycline is anti-inflammatory and inhibits Staphylococcal exotoxin-induced cytokines and chemokines, Antimicrob. Ag. Chemother., 47(11), pp. 3630-3633, 2003].

b. Source: Doxycycline is a semisynthetic antibiotic that is obtained from . [Schepdael, A., Kibaya, R., Roets, E., Hoogmartens, Analysis of Doxycycline by Capillar Electrophoresis, Chromatograhia, 41(5/6), pp. 367-369, 2005].

c. Cell line Test (MIC): In this study, Doxycycline was used to treat Q fever endocarditis caused by Coxiella burnetti. This antibiotic was shown to inhibit the growth of this bacterium at different minimum concentriations between 1-8 µg/mL. [Rolain, J., Boulos, A., Mallet, M., Raoult, D., Correlation between ratio of serum doxycycline concentration to MIC and rapid decline of antibody levels during treatment of Q fever endocarditis, Antimicrob. Ag. Chemother., 49(7), pp. 2673-2676, 2005]. d. Human clinical trials: In this study, doxycycline and azithromycin were used to test their effects against malaria in patients caused by Plasmodium falciparum in the Saradidi Rural Health Development Project. [Andersen, S., Oloo, A., Gordon, D., Ragama, O., Aleman, G., Berman, J., Tang, D., Dunne, M., Shanks, G., Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycline as propyhylaxis for malaria in Western Kenya, Clin. Infect. Dis. 26(1), pp. 146-150, 1998].

e. Review Article: In this study, Doxycycline effects on Staphylococcal superantigen activation and cytokine production. [Krakauer, T., Buckley, M., Doxycycline is anti-inflammatory and inhibits Staphylococcal exotoxin- induced cytokines and chemokines, Antimicrob. Ag. Chemother., 47(11), pp. 3630-3633, 2003].

Antibiotic name Diseases treated m log P Enoxacin Gonorrhea and cancer = -0.381

SMILESFc1c(nc2c(c1)C(=O)C(\C(=O)O)=C/ IUPAC MIC values N2CC)N3CCNCC3 1-ethyl-6-fluoro-4-oxo-7- 1.25 mg/L against tuberculosis (piperazin-1-yl)-1,4-dihydro-1,8- naphthyridine-3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

320.319 g/mol,C15H17FN4O3 Fluoroquinolones Enoxen, Enroxil

Dipole Moment (Debye) Molecular Volume Surface Area 7.81 Debye 303.68 A3 323.74 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 2 87.461 A 74011-58-8 0.0257 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 7 2

References and summary a. MOAThe mechanism of action for enoxacin is DNA gyrase inhibition (They block the twisting in DNA). (Yoshida, H., et al. "Mechanism of action of quinolones against Escherichia coli DNA gyrase." Antimicrobial agents and chemotherapy 37.4 (1993): 839-845.)

b. SourceEnoxacin is a synthetic drug. (Niki, Yoshihito, et al. "New synthetic quinolone antibacterial agents and serum concentration of theophylline." CHEST Journal 92.4 (1987): 663-669.)

c. Cell line Test (MIC)Enoxacin has a MIC value of 1.25 mg/l or less for strains of Mycobacterium tuberculosis. (Davies, S., P. D. Sparham, and R. C. Spencer. "Comparative in-vitro activity of five fluoroquinolones against mycobacteria." Journal of Antimicrobial Chemotherapy 19.5 (1987): 605-609.)

d. Human clinical trialsEnoxacin was tested against urinary tract infections on 40 patients receiving 200 mg and 40 patients receiving a placebo. (Desai, K. M., P. H. Abrams, and L. O. White. "A double-blind comparative trial of short-term orally administered enoxacin in the prevention of urinary infection after elective transurethral prostatectomy: a clinical and pharmacokinetic study." The Journal of urology 139.6 (1988): 1232-1234.)

e. Review Article(Jaber, L. A., E. M. Bailey, and M. J. Rybak. "Enoxacin: a new fluoroquinolone."Clinical pharmacy 8.2 (1989): 97-107.) f. (Khaliq, Yasmin, and George G. Zhanel. "Fluoroquinolone-associated tendinopathy: a critical review of the literature." Clinical infectious diseases36.11 (2003): 1404-1410.)

Antibiotic name Diseases treated m log P Ertapenem Urinary Tract and Lung Infections = 0.93

SMILES IUPAC MIC values

O=C(O)c1cc(ccc1)NC(=O)[C@H]4N (4R,5S,6S)-3-[(3S,5S)-5-[(3- 0.002 to 0.125 μg/ml (Neisseria C[C@@H](S\C3=C(\N2C(=O)[C@H] carboxyphenyl)carbamoyl] gonorrhoeae) ([C@H](O)C)[C@H]2[C@H]3C)C(= pyrrolidin-3-yl]sulfanyl-6-(1- O)O)C4 hydroxyethyl)-4-methyl-7- oxo-1-azabicyclo[3.2.0]hept- 2-ene-2-carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C22H25N3O7S, 475.522 g/mol Carbapenem Invanz

Dipole Moment (Debye) Molecular Volume Surface Area 6.39 Debye 445.44 Å3 471.96 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 143.321 Å2 153832-46-3 0.0143 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 5 10

References and summary a. MOA Inhibits the cell wall synthesis in bacterial organisms.(Nagano, R., et al., In vitro antibacterial activity and mechanism of action of J-111,225, a novel 1β-methylcarbapenem, against transferable IMP-1 metallo-β- lactamase producers, Journal of Antimicrobial Chemotherapy, Vol. 45, p. 271-276, 2000)

b. Source All carbapenems are derived from Streptomyces cattleya.(Nunez, L., et al., The Biosynthetic Gene Cluster for the β-Lactam Carbapenem Thienamycin in Streptomyces cattleya, Science & Biology, Vol. 10, Issue 4, p. 301-311, 2003)

c. Cell line Test (MIC) When inhibiting Neisseria gonorrhoeaee, 0.002 to 0.125 μg/ml is recommended.(Unemo, M., et al., In Vitro Activity of Ertapenem versus Ceftriaxone against Neisseria gonorrhoeae Isolates with Highly Diverse Ceftriaxone MIC Values and Effects of Ceftriaxone Resistance Determinants: Ertapenem for Treatment of Gonorrhea?, Antimicrobial Agents and Chemotherapy, Vol. 56, No. 7, p. 3603-3609, 2012) d. Human clinical trials Treatment of intra-abdominal infections with Ertapenem.(DiNubile, M., et al., Bowel colonization with resistant gram-negative bacilli after antimicrobial therapy of intra-abdominal infections: observations from two randomized comparative clinical trials of ertapenem therapy, European Journal of Clinical Microbiology and Infectious Diseases, Vol. 24, Issue 7, p. 443-449, 2005) e. Review Article Review article pertaining to the ability of Ertapenem to treat blood infections.(Collins, V., et al., Efficacy of Ertapenem for Treatment of Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase- Producing Enterobacteriaceae, Antimicrobial Agents and Chemotherapy, Vol. 56, No. 4, p. 2173-2177, 2012)

Antibiotic name Diseases treated m log P Erythromycin Treats respiratory tract infection =2.281

SMILES IUPAC MIC values CC[C@@H]1[C@@]([C@@H]([C@H]( (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R) 0.25 µg/ mL when tested on the -6- {[(2S,3R,4S,6R)-4-(dimethylamino)- C(=O)[C@@H](C[C@@]([C@@H]([C intercellular assay L. Pneumophila 3-hydroxy-6-methyloxan-2-yl]oxy}- 14- @H]([C@@H]([C@H](C(=O)O1)C)O[C ethyl-7,12,13-trihydroxy-4- @H]2C[C@@]([C@H]([C@@H](O2)C) {[(2R,4R,5S,6S)- 5-hydroxy-4-methoxy- O)(C)OC)C)O[C@H]3[C@@H]([C@H]( 4,6-dimethyloxan-2-yl]oxy}- C[C@H](O3)C)N(C)C)O)(C)O)C)C)O)( 3,5,7,9,11,13-hexamethyl-1- C)O oxacyclotetradecane-2,10-dione Emp. Formula, Molar mass Antibiotic group Trade names C37H67NO13, 733.93 g/mol Macrolide Antibiotic Erasis

Dipole Moment (Debye) Molecular Volume Surface Area 2.80 Debye 748.54 Å3 711.32 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 193.924 Å2 114-07-8 0.00374 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 5 5

References and summary a. MOA The mechanism of action is inhibiting the growth of the bacteria. (Desaki, Masashi, et al. "Molecular mechanisms of anti-inflammatory action of erythromycin in human bronchial epithelial cells: possible role in the signaling pathway that regulates nuclear factor-κB activation." Antimicrobial agents and chemotherapy 48.5 (2004): Page 1581-1585)

b. Source The source of Erthromycin is being made from natural products mixed with semisynthetic modification. (Newman, David J., Gordon M. Cragg, and Kenneth M. Snader. "Natural products as sources of new drugs over the period 1981-2002." Journal of natural products 66.7 (2003): Pages 1022- 1037.)

c. Cell line Test (MIC) The MIC value was 0.25 µg/ mL when tested on the intercellular assay L. Pneumophila to check for how effective the drug is against bacteria. (Stout, Janet E., Beth Arnold, and V. L. Yu. "Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin, quinupristin/dalfopristin and erythromycin against Legionella species by intracellular susceptibility testing in HL-60 cells." Journal of Antimicrobial Chemotherapy 41.2 (1998): Pages 289-291.) d. Human clinical trials The Effect of Concomitant Administration of Erythromycin and Diltiazem on CYP3A Activity in Healthy Volunteers. The purpose of the test was to observe the effects of the drug when the two drugs are taken simultaneously, and individually. The drug had completed phase 4 in 2007.

e. Review Article Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes.( Ray, Wayne A., et al. "Oral erythromycin and the risk of sudden death from cardiac causes." New England Journal of Medicine 351.11 (2004): 1089-1096.) This article is about oral Erythromycin having high rate of death caused my taking high dosages of the drug. f.

Antibiotic name Diseases treated m log P Ethambutol Tuberculosis =0.35

SMILES IUPAC MIC values CC[C@@H](CO)NCCN[C@@H](CC)CO (2S,2’S)-2,2’-(Ethane-1,2- ≥ 20 µg/mL when tested for diyldiimino)dibutan-1-ol Mycobacteriam tuberculosis mutations

Emp. Formula, Molar mass Antibiotic group Trade names C10H24N2O2, 204.31 g/mol Bacteriostatic Antimycobacterial Myambutol, Servambutol.

Dipole Moment (Debye) Molecular Volume Surface Area 1.95 Debye 237.77 Å3 61.39 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 64.51 Å2 74-55-5 0.008 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 4 4

References and summary a. MOA Ethambutol obstructs arabinosyl transferases which helps in cell wall biosynthesis. By obstructing this enzyme, the bacterial cell wall complex production is repressed. This leads to an escalation in cell wall permeability. (drug bank .com.

b. Source Ethambutol is a sythetic drug ( Chemical Entities of Biological Interest. UK: European Bioinformatics Institute,2010.)

c. Cell line Test (MIC) An MIC value of ≥ 20 µg/mL when tested for Mycobacteriam tuberculosis mutations. (Sreevatsan, S., et al. Ethambutol resistance in Mycobacterium tuberculosis: critical role of embB mutations, Antimicrobial agents and chemotherapy, (41)8 , p. 1677-1681.1997.)

d. Human clinical trials This study was carried out to develop specific radiopharmaceutical and to estimate its efficiency in human to detect and locate the tubercular lesion using Ethambutol. (Namrata S., et al. Clinical Evaluation of Efficacy of 99mTC -Ethambutol in Tubercular Lesion Imaging, Tuberculosis Research and Treatment, p.9 , 2010.)

e. Review Article A review of the use of ethambutol in children was carried out. (Trebucq, A.,Should ethambutol be recommended for routine treatment of tuberculosis in children? A review of the literature, The International Journal of Tuberculosis and Lung Disease, (1)1, p. 12-15, 1997)

Antibiotic name: Diseases treated: m log P= Ethionamide tuberculosis 1.46

SMILES: IUPAC: MIC values: CCC1=NC=CC(=C1)C(N)=S 2-ethylpyridine -4- 0.25µg/mL against M.tuberculosis

carbothioamide

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C8H10N2S, 166.249 g/mol Pyridines Trecator

Dipole Moment (Debye)= Molecular Volume= Surface Area= 4.74 Debye 152.4 Å3 195.81 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 38.915 Å2 536-33-4 0.0311 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N): atoms): 1 1

References and summary a. MOA: Ethionamide has the same mechanism of action as . Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.( Winder, FRANK G. "Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of the mycobacteria." The biology of the mycobacteria 1 (1982): 353-438.) b. Source: Ethionamide is derived from Isonicotinic acid. (Hallbauer, Ute M., and H. Simon Schaaf. "Ethionamide- induced hypothyroidism in children: original research." Southern African Journal of Epidemiology and Infection 26.3 (2011): 161-163.)

c. Cell line Test (MIC): In this cell line test Molecular Investigation of Resistance to the Antituberculous Drug Ethionamide in Multidrug-Resistant Clinical Isolates of Mycobacterium tuberculosis. Mutation in 87 clinical isolates were searched 47 ETH-resistant (ETHr) isolates, 24 ETH-susceptible (ETHs) isolates, and 16 isolates susceptible to ETH but displaying an intermediate proportion of resistant cells. (Brossier, F., et al. "Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug-resistant clinical isolates of Mycobacterium tuberculosis." Antimicrobial agents and chemotherapy 55.1 (2011): 355-360.) d. Human clinical trials: Two clinical trials concerning this topic have been reported. A controlled retreatment trial with various combinations of ethionamide, cycloserine, and pyrazinamide with and without conventional "low" doses of isoniazid (300 mg per day) showed no benefit when isoniazid was added. However, a noncontrolled trial using ethionamide and pyrazinamide with and without high doses of isoniazid, 1 to 1.5 g per day, showed marked benefit with the added isoniazid.( Moulding, T. S. "Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance?." The American review of respiratory disease 123.3 (1981): 262-264.) e. Review Article: Winder, FRANK G. "Mode of action of the antimycobacterial agents and associated aspects of the molecular biology of the mycobacteria." The biology of the mycobacteria 1 (1982): 353-438. Hallbauer, Ute M., and H. Simon Schaaf. "Ethionamide-induced hypothyroidism in children: original research." Southern African Journal of Epidemiology and Infection 26.3 (2011): 161-163. Brossier, F., et al. "Molecular investigation of resistance to the antituberculous drug ethionamide in multidrug- resistant clinical isolates of Mycobacterium tuberculosis." Antimicrobial agents and chemotherapy 55.1 (2011): 355- 360. Moulding, T. S. "Should isoniazid be used in retreatment of tuberculosis despite acquired isoniazid resistance?." The American review of respiratory disease 123.3 (1981): 262-264. f.

Antibiotic name Diseases treated Clostridium m log P Fidaxomicin difficile-associated diarrhea = 8.245

SMILES IUPAC MIC values

CC[C@H]1/C=C(/[C@H](C/C=C/C=C(/C(=O 3-(((6-Deoxy-4-O-(3,5-dichloro-2-ethyl-4,6- 0.25 μg/mL when tested for inhibition dihydroxybenzoyl)-2-O-methyl-β-D- )O[C@@H](C/C=C(/C=C(/[C@@H]1O[C@ against Clostridium difficile mannopyranosyl)oxy)-methyl)-12(R)-[(6- H]2[C@H]([C@H]([C@@H](C(O2)(C)C)OC( deoxy-5-C-methyl-4-O-(2-methyl-1-

=O)C(C)C)O)O)\C)\C)[C@@H](C)O)\CO[C oxopropyl)-β-D-lyxo-hexopyranosyl)oxy]- 11(S)-ethyl-8(S)-hydroxy-18(S)-(1(R)- @H]3[C@H]([C@H]([C@@H]([C@H](O3) hydroxyethyl)-9,13,15- C)OC(=O)C4=C(C(=C(C(=C4O)Cl)O)Cl)CC)O trimethyloxacyclooctadeca-3,5,9,13,15-

)OC)O)\C pentaene-2-one Emp. Formula, Molar mass Antibiotic group Trade names C52H74Cl2O18, 1058.04g/mol Macrocyclics Dificid

Dipole Moment (Debye) Molecular Volume Surface Area 4.13 debye 353.62 Å3 96.331 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 266.681 Å2 873857-62-6 0.0117 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 15 available, attached to O, S, N) atoms) 7 18

References and summary a. MOA Fidaxomicin inhibits the translation of Clostridium difficile. ( Leeds, J. A., et al. Mechanism of action of and mechanism of reduced susceptibility to the novel anti-Clostridium difficile compound LFF571. Antimicrobial agents and chemotherapy (56)8 p. 4463-4465, 2012).

b. Source Fidaxomicin is a fermented compound gotten from the actinomycete Dactylosporangium aurantiacum subspecies hamdenesis. (Fidaxomicin. Drugs in R&D (10) 1, p. 37-45, 2012).

c. Cell line Test (MIC) A cell line test of 0.25 μg/mL was carried out to test for inhibition against Clostridium difficile. (Farah, B., Laurent, B., Abraham, G., Pamela, S., Ly, N., Abraham, L., Fidaxomicin Inhibits Spore Production in Clostridium difficile. Oxford Journals. (55)2, p.162-169, 2012).

d. Human clinical trials A clinical trial was carried out to determine the efficiacy of Fidaxomicin versus Vancomycin. (Tannock, Gerald W., et al. A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin. Microbiology (156)11, p. 3354-3359, 2010).

e. Review Article A review of literature carried out on patients on the efficacy of Fidaxomicin in managing Clostridium difficile infections. (Lancaster, W., et al. Fidaxomicin: The Newest Addition to the Armamentarium Against< i> Clostridium difficile Infections. Clinical therapeutics, (34)1 p. 1-13, 2012).

Antibiotic nameFlucloxacillin Diseases treated Chest, ear, nose m log P and throat infections 2.778

SMILES IUPAC(2S,5R,6R)-6-({[3-(2- MIC values 0.25-0.375 µg/ml, sensitive O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O chloro-5-fluorophenyl)-5- staphylococci )c2c(onc2c1c(F)cccc1Cl)C)[C@H]4SC3(C)C methylisoxazole-4- yl]carbonyl}amino)-3,3-dimethyl- 7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar Antibiotic groupPenicillins Trade namesFlopen massC19H17ClFN3O5S, 453.87 g/mol

Dipole Moment (Debye)3.23 Debye Molecular Volume354.6 Å3 Surface Area444.50 Å2

Surface Area (TPSA) 112.738 Å2 CAS Number5250-39-5 D/V (dipoe moment/volume)0.009 Debye/ Å3

Rotatable # bonds4 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 2 atoms)8

References and summary a. MOA Inhibits the synthesis of bacterial cell walls. It inhibits cross-linkage between linear peptidoglycan polymer chains which can make up the major component of the cell wall of Gram-positive bacteria. (Rossi , S. Australian Medicines. Adelaide: Australian Medicines Handbook; 2006.)

b. Source Originated from the Penicillium fungi. (Garrod, L. P. Relative Antibacterial Activity of Three Penicillins. British Medical Journal (5172): 527–29, 1990

c. Cell line Test MIC= 0.25-0.375 mg/L against sensitive staphylococci. (Drusano, G., et al. Population Pharmacokinetics at Two Dose Levels and Pharmacodynamic profiling of . Antimicrobial Agents and Chemotherapy. 51 (9); p. 3290-3297, 2007) (MIC)

d. Human clinical In this randomized trial the efficacy, safety, and length of hospital stay for pateints with staphylococcal infections treated with either fluoroquinolone plus or with flucloxacillin is compared. (Schrenzel, J., et al. A randomized Clinical Triial to Compare -Rifampicin with Flucloxacillin or Vancomycin for the treatment of Staphylococcal Infection. Clinical Infectious Disease. 39 (9); p. 1285-1292, 2004) trials

e. Review Article(Sutherland, R.E. Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin. BMJ; 4:455-460, 1980)

Antibiotic name Flumequine Diseases treated Bacterial miLogP 0.456 infections

SMILES IUPAC 7-fluoro-12-methyl-4- MIC values 0.49 µg/ml against bacteria Fc2cc1C(=O)/C(C(=O)O)=C \N3c1c(c2)CCC oxo-1- associated with scallops larvae (Pecten 3C azatricyclo[7.3.1.05,13]trideca- maximus) 2,5,7,9(13)-tetraene-3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Quinolone- 1st Trade names Flubactin C14H12FNO3 261.25 g/mol Generation

Dipole Moment (Debye) 8.69 Debye Molecular Volume 244.16 Å3 Surface Area 253.08 Å2

Surface Area (TPSA) 59.304 Å2 CAS Number 42835-25-6 D/V (dipoe moment/volume) 0.0355 Debye/ Å3

Rotatable # bonds 1 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 4 atoms) 1

References and summary a. MOA It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV. (Drlica K, Zhao X. 1997. "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiology and Molecular Biology Reviews 61:377–92)

b. Source Flumequine is a synthetic chemotherapeutic antibiotic of the drug class: fluoroquinolone. (Nelson JM, Chiller TM, Powers JH, Angulo FJ. 2007. "Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story". Clinical Infectious Diseases 44: 977–80

c. Cell line Test In a study, it is concluded that flumequine is, to a varying degree, antagonized by components in sea water. In addition, the MIC values increased significantly using 25% sea water compared to 2% NaCl. (Torkildsen, L., Samuelsen, O. B., Lunestad, B. T., & Bergh, Ø. 2000. Minimum inhibitory concentrations of chloramphenicol, , trimethoprim/sulfadiazine and flumequine in seawater of bacteria associated with scallops (Pecten maximus) larvae. Aquaculture, 185:1-12. (MIC) d. Human clinical Quinolones are able to induce CNS reactions in 0.9–2.1% of cases, but severe reactions occur in less than 0.5%. Only Flumequine and fleroxacin have produced convulsions in animals after systemic administration. (Christ, W. (1990). Central nervous system toxicity of quinolones: human and animal findings. Journal of Antimicrobial Chemotherapy, 26: 219-225.) trials

e. Review Article Fluoroquinolones antibiotics are more effective towards pathogens resistant to other antibacterials, thus being regularly prescribed drugs in human and veterinary medicine. (Samanidou, V. F., Christodoulou, E. A., & Papadoyannis, I. N. 2005. Recent Advances in Analytical Techniques used for the Determination of Fluoroquinolones in Pharmaceuticals and Samples of Biological Origin-A Review Article. Current Pharmaceutical Analysis, 1:155-193.)

Antibiotic name Diseases treated m log P Furazolidone enteritis and diarrhea =0.828

SMILES IUPAC MIC values [O -][N+](=O)c2oc(C=NN1C(=O)OCC1)cc2 3-{[(5-nitro-2- <0.048-0.78 μg/ml, Campylobacter fetus furyl)methylene]amino}-1,3- <0.048-0.78 µg/ml, Campylobacter fetus oxazolidin-2-one

Emp. Formula, Molar mass Antibiotic group Trade names

C8H7N3O5, 225.16 g/mol Furoxone

Dipole Moment (Debye) Molecular Volume Surface Area 7.65 Debye 196.55 Å3 228.38 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 100.871 Å2 67-45-8 0.04 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 0 0

References and summary a. MOA The mechanism of action for furazolidone was determined to be bining of bacterial DNA. This leads to the inhibition of monoamine oxidase. (Pollock, B., et al, Topical aminolaevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action, BJD, 151(3), p. 616-622, 2004)

b. Source Furazolidone is a synthetic antibiotic. (Herrlich, P., et al, , a group of synthetic antibiotics, with a new mode of action: discrimination of specific messenger RNA classes, PNAS, 73(10), p. 3386-3390, 1976)

c. Cell line Test (MIC) <0.048-0.78 μg/ml, Campylobacter fetus (Vanhoof, R. et al, Bacteriostatic and bactericidal activities of 24 antimicrobial agents against Campylobacter fetus subsp. jejuni., Antimicrob. Agents Chemother., 18(1), p. 118- 121, 1980)

d. Human clinical trials A double blind study was conducted to test the effectiveness of furazolidone when treating for Helicobacter pylori chronic gastritis. (Xiao, S., et al, The efficacy of furazolidone and metronidazole in the treatment of chronic gastritis associated with Helicobacter (Campylobacter) pylori--a randomized double-blind placebo-controlled clinical trial, JGH, 37(5), p. 503-506, 1990)

e. Review Article Clinical studies suggest that furazolidone has good short-term and long-term effects concerning the treatment of ulcers. (Zheng, Z., et al, Treatment of peptic ulcer disease with furazolidone, JGH, 7(5), p. 533-537, 1992)

Antibiotic name Fusidic Acid Diseases treatedGram positive m log P bacteria 5.947

SMILES IUPAC 1S,2S,5R,6S,7S,10S,11S,13 MIC values2.06 µg/ml, bacterial isolates

O=C(O)/C(=C3/[C@@H]2C[C@@H](O) S,14Z,15R,17R)-13-(acetyloxy)-

[C@H]1[C@@]4(C)CC[C@@H](O)[C@ 5,17-dihydroxy-2,6,10,11- @H](C)[C@@H]4CC[C@@]1([C@]2(C tetramethyltetracyclo[8.7.0.02,7.01 [C@@H]3OC(=O)C)C)C)CC \C=C(/C)C 1,15]heptadecan-14-ylidene]-6- methylhept-5-enoic acid

Emp. Formula, Molar mass Antibiotic groupHydroxysteroids Trade names Fucidin

C31H48O6 , 516.709 g/mol

Dipole Moment (Debye)1.76 Debye Molecular Volume512.753 Å3 Surface Area446.28 Å2

Surface Area (TPSA) 104.06 Å2 CAS Number6990-06-3 D/V (dipoe moment/volume) 0.003 Debye/Å3

Rotatable # bonds6 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)3 atoms)6

References and summary a. MOA Fusidic acid is a protein synthesis inhibitor that prevents the turnover of elongation factor G from ribosome. (Lec lercq R, et. al. In Vitro Activity of Fusidic Acid Against Streptococci isolated form skin and soft tissue infections. J. Antimicrob. Chemother. 45 (1); p. 27-29, 2000)

b. Source Fusidic acid derived from the fungus Fusidium coccineum. (Falagas M., et. al., A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev. Anti Infection Therapy. 6(5); p. 563-600, 2008)

c. Cell line Test The MIC=2.06 µg/ml for Fusidic acid against bacterial isolates. (Kronvall, G., MIC determination of fusidic acid and of ciprofloxacin using multidisc diffusion tests. Clin Microbiol Infect. 6(9):p. 483-489. 2000) (MIC)

d. Human clinical trials Fusidic acid was used to control the antileprosy activity in nine lepromatous leprosy patients. Patients received 500 mg/day for 8 weeks. (Franzblau, S., et. al, Clinical trial of fusidic acid for lepromatous leprosy. Antimicrob Agents Chemother. 38(7): 1651–1654, 1994)

e. Review Article(Helmut, S., et al. Fusidic Acid in dermatology. European Journal of Dermatology. 20 (1); p. 6-15, 2010)

Antibiotic name Gatifloxacin Diseases treated Treats m log P -0.036 conjunctivitis ("pink eye")

SMILES IUPAC 1-cyclopropyl-6-fluoro- MIC values Gatifloxacin was highly

Fc1c(c(OC)c2c(c1)C(=O)C(\C(=O)O)=C/N2 8-methoxy-7-(3- potent (MIC90s, 0.03–0.06 mg/L) against C3CC3)N4CC(NCC4)C methylpiperazin-1-yl)- 4-oxo- Haemophilus influenzae, Legionella spp quinoline-3-carboxylic acid

rd Emp. Formula, Molar mass C19H22FN3O4 Antibiotic group Quinolone- 3 Trade names Tequin, Zymar 375.394 g/mol Generation

Dipole Moment (Debye) 4.94 Debye Molecular Volume 366.83 Å3 Surface Area 384.42 Å2

Surface Area (TPSA) 83.803 Å2 CAS Number 112811-59-3 D/V (dipoe moment/volume) 0.0135 Debye/ Å3

Rotatable # bonds 4 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 2 atoms) 7

References and summary a. MOA It inhibits the bacterial enzymes DNA gyrase and topoisomerase IV. (Burka JM, Bower KS, Vanroekel RC, Stutzman RD, Kuzmowych CP, Howard RS. 2005 . "The effect of fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial healing following photorefractive keratectomy". Am. J. Ophthalmol. 140: 83–7)

b. Source The quinolones are a family of synthetic broad-spectrum antibacterial drugs. Gatifloxacin is a fluoroquinolone so it has a fluorine atom attached to the central ring system, typically at the 6-position or C-7 position. (Andersson, MI, MacGowan, AP. 2003. Development of the quinolones. J. Antimicrob. Chemother. 51:1– 11)

c. Cell line Test Gatifloxacin is a broad-spectrum 8-methoxy fluoroquinolone that is more potent than ciprofloxacin and ofloxacin against Gram-positive bacteria, chlamydia, mycoplasma, mycobacteria and anaerobes.( Fung-Tomc, J., Minassian, B., Kolek, B., Washo, T., Huczko, E., & Bonner, D. 2000. In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin. Journal of Antimicrobial Chemotherapy, 45: 437-446.) (MIC)

d. Human clinical Both topical moxifloxacin 0.5% and gatifloxacin 0.3% penetrated the vitreous in the uninflamed eye, but the vitreous concentrations attained were all lower than the 90% minimum inhibitory concentration for the commonest bacterial pathogens causing acute postoperative endophthalmitis. (Costello, P., Bakri, S. J., Beer, P. M., Singh, R. J., Falk, N. S., Peters, G. B., & Melendez, J. A. (2006). Vitreous penetration of topical moxifloxacin and gatifloxacin in humans. Retina, 26(2), 191-195.) trials

e. Review Article Fourth-generation quinolones, such gatifloxacin (Tequin), have become widely used in outpatient and inpatient settings. These quinolones add Gram-positive bacterial coverage and maintain the Gram-negative coverage of earlier quinolones. This broad-spectrum coverage has numerous clinical applications, such as respiratory, gastrointestinal, or urinary systems infections. (Biggs, W. S. 2003. Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients. The Journal of the American Board of Family Practice, 16(5), 455-457.)

Antibiotic name Diseases treated m log P Geldanamycin Huntington’s and Parkinson Dis. =0.429

SMILES IUPAC MIC values NC(=O)O[C@H]1C(/C)=C/[C@H](C)[C@@ (4E,6Z,8S,9S,10E,12S,13R,14S,16R)- 6.4 mg/L, Candida albicans H](O)[C@@H](OC)C[C@H](C)C \C2=C(/OC 13-hydroxy )C(=O) \C=C(\NC(=O)C(\C)=C\C=C/[C@@H -8,14,19-trimethoxy-4,10,12,16- ]1OC)C2=O tetramethyl -3,20,22-trioxo-2-azabicyclo[16.3.1] docosa-1(21),4,6,10,18-pentaen-9- yl carbamate Emp. Formula, Molar mass Antibiotic group Trade names C29H40N2O9, 560.644 g/mol Benzoquinone ansamycins N/A

Dipole Moment (Debye) Molecular Volume Surface Area 2.44 Debyes 570.97 Å3 585.35 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 163.498 Å2 30562-34-6 0.00427 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 4 11

References and summary a. MOA: Geldanamycin functions by creating free radicals, and inhibiting tyrosine kinases and heat shock proteins (90). [Ochel, H., Eichhorn, K., Gademann, G., Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones, Cell Stress and Chaperones, 6(2), pp. 105-112, 2001].

b. Source: Geldanamycin was isolated from the bacteria, Streptomyces hygroscopicus, in 1970.[Ochel, H., Eichhorn, K., Gademann, G., Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones, Cell Stress and Chaperones, 6(2), pp. 105-112, 2001].

c. Cell line Test (MIC): In study, Geldanamycin was used to determine its MIC against different species of Candida. Against Candida albicans, Geldanamycin had a MIC value of 6.4mg/L. [Zhang, J., Liu, W., Tan, J., Sun, Y., Wan, Z., Li, R., Antifungal activity of geldanamycin alone or in combination with fluconazole against Candida species, Mycopathologia, 173, pp. 273-279, 2013].

d. Human clinical trials: In this clinical trial, 17-DMAG, a derivative of geldanamycin, was used to treat patients with solid tumors at the University of Pittsburgh Cancer Institute and Memorial Sloan Kettering Cancer Center. [Aregbe, A., Sherer, E., Egorin,M., Scher,H., Solit,D., Ramanathan, R., Ramalingam,S., Belani, C., Ivy, P., Bies, R., Population pharmacokinetic anyalysis of 17-dimethylaminoethylamino-17-demthoxygedamnamycin (17-DMAG) in adult patients with solid tumors, Cancer Chemother. Pharmacol., 70, pp.201-205, 2012].

e. Review Article: The history, structure, activity, and properties of geldanamycin are provided in this article. [Ochel, H., Eichhorn, K., Gademann, G., Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones, Cell Stress and Chaperones, 6(2), pp. 105-112, 2001].

Antibiotic name Diseases treated : Chronic bronchitis, m log P Gemifloxacin mild-to-moderate pneumonia = -0.757

SMILES IUPAC MIC values Fc2c(nc1N(/C=C(/C(=O)O)C(=O)c1c2)C3CC 7-[(4Z)-3-(Aminomethyl)-4- S. aureaus 0.03 mg/L 3)N4C/C(=N \OC)C(C4)CN methoxyimino-pyrrolidin-1-yl]-1- E. coli 0.13 mg/L cyclopropyl-6-fluoro-4-oxo- 1,8- H. influenza 0.002 mg/L naphthyridine-3-carboxylic acid M. catarrhalis 0.016 mg/L

Emp. Formula, Molar mass Antibiotic group Trade names nd C18H20FN5O4 389.381 g/mol Quinolone (2 generation) Factive

Dipole Moment (Debye) Molecular Volume Surface Area 5.55 Debye 368.88 Å3 399.58 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 98.715 Å2 175463-14-6 0.015 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 3 10

References and summary a. MOA: Gemifloxacin functions as an antibiotic by inhibiting bacterial DNA gyrase and topoisomerase IV. (Chen, Tun-Chieh, et al. "Gemifloxacin Inhibits Migration And Invasion And Induces Mesenchymal-Epithelial Transition In Human Breast Adenocarcinoma Cells." Journal Of Molecular Medicine (Berlin) 92.1 (n.d.): 53-64)

b. Source: Gemifloxacin is a synthetic antibiotic. The intermediate gemifloxacin the chemoselective hydrogenation of 4-cyano- 3 – methoxyimino-1-(N-tert- butoxycarbonyl) pyrrolidine. (H. K., Noh, et al. "Synthesis Of The Intermediate Of Gemifloxacin By The Chemoselective Hydrogenation Of 4- Cyano-3-Methoxyimino-1-(N-Tert-Butoxycarbonyl)Pyrrolidine. Part 2. The Palladium Catalysts In Acidic Media." Organic Process Research & Development 8.5 (2004): 788.)

c. Cell line Test For this cell line test gemifloxaci’s photochemical clastogenic potential was assessed against cultured CHL cells and compared to 11 other quinolones. The MIC value was found to be less than 30μg/ml. (Satoru, Itoh, Nakayama Shiho, and Shimada Hiroyasu. "In Vitro Photochemical Clastogenicity Of Quinolone Antibacterial Agents Studied By A Chromosomal Aberration Test With Light Irradiation." Mut.Res.-Genetic Toxicology And Environmental Mutagenesis 517.(n.d.): 113-121) (MIC) d. Human clinical trials : Gemifloxacin was tested in combination with Azithromycin and Gentamicin in a variety of regimens as a treatment for uncomplicated cervical or urethral gonorrhea. (Pereira, Rui, Michelle J. Cole, and Catherine A. Ison. "Combination Therapy For Gonorrhoea: In Vitro Synergy Testing." Journal Of Antimicrobial Chemotherapy (JAC) 68.3 (2013): 640-643)

e. Review Article : Due to the development of multidrug-resistance Streptococcus pneumonia to macrolides and β- lactam bacteria, gemifloxacin along with other fluoroquinolones was recommended for treatment. (Fuller, Jeffrey D., and Donald E. Low. "A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance." Clinical infectious diseases 41.1 (2005): 118-121.)

Antibiotic name Diseases treated m log P Gentamicin Treats Gram-negative infections =-4.123

SMILES IUPAC(3R,4R,5R)-2- MIC values O[C@]3(C)[C@H](NC)[C@@H](O)[ {[(1S,2S,3R,4S,6R)-4,6- 4 µg/mL for patients infected with C@@H](O[C@H]2[C@H](N)C[C@ diamino-3-{[(2R,3R,6S)- Enterococcus l 3-amino-6-[(1R)- H](N)[C@@H](O[C@H]1O[C@H](C 1-(methylamino)ethyl]oxan-2-

(NC)C)CC[C@H]1N)[C@@H]2O)O yl]oxy}- C3 2-hydroxycyclohexyl]oxy}-5- methyl- 4-(methylamino)oxane-3,5-diol Emp. Formula, Molar mass Antibiotic group Trade names

Emp. Formula C21H43N5O7 Aminogylcoside Garamycin Mass 477.603 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 5.46 Debye 474.11Å2 490.40Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 166.290Å2 1403-66-3 0.0115 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 11 12

References and summary a. MOAThe mechanism of action is by binding the 30S subunit of a bacterial ribosome by interrupting the synthesis of its protein. The mechanism is similar to the moa’s of other .( Imamovic, Lejla, and Morten OA Sommer. "Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development." Science translational medicine 5.204 (2013): 204ra132-204ra132.)

b. SourceThe drug is derived from an aminoglycoside.( Avent, M. L., et al. "Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity." Internal medicine journal 41.6 (2011): 441-449.)

c. Cell line Test (MIC) The cell line test discovered was 4µg/mL when test on infected people.( Chow, Joseph W., et al. "A novel gentamicin resistance gene in Enterococcus." Antimicrobial agents and chemotherapy 41.3 (1997): 511-514.)

d. Human clinical Local Gentamicin Application to Reduce Postoperative Infection Rate in Hemiarthroplasty After Fracture of the Proximal Femur: a Randomized Controlled Trial trials Completed Phase 3

e. Review ArticleDahlgren, James G., Elizabeth T. Anderson, and William L. Hewitt. "Gentamicin blood levels: a guide to nephrotoxicity." Antimicrobial Agents and Chemotherapy 8.1 (1975): 58-62. The article is about test done on patients who have low gentamicin blood levels.

Antibiotic name Diseases treated m log P Grepafloxacin Gastrointestinal disease, bronchitis =2.172

SMILES IUPAC MIC values O=C(O) \C2=C\N(c1cc(c(F)c(c1C2=O)C)N3C (RS)-1-cyclopropyl-6-fluoro-5- 0.001-3 mg/L, P. aeruginosa C(NCC3)C)C4CC4 methyl-7-(3-methylpiperazin-1- yl)- 4-oxo-quinoline- 3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C19H22FN3O3, 359.395 g/mol Flouroquinolones Raxar

Dipole Moment (Debye) Molecular Volume Surface Area 6.44 Debye 355.93 Å3 368.91 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 74.569 Å2 119914-60-2 0.018 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA Grepafloxacon selectively inhibits DNA gyrase and topoisomerase II ligase domain. (Hooper, D., Quinolone: Mode of Action, Drugs, 49(2) p. 10-15, 1995)

b. Source The natural source of Grepafloxacin is quinine, a natural white crystalline alkaloid. (Forrest, A., et al., Pharmacokinetics and pharmacodynamics of oral grepafloxacin patients with acute bacterial exacerbations of chronic bronchitis, J. Antimicro. Chemother., 40, p. 45-57, 1997)

c. Cell line Test (MIC) 0.001-3 mg/L, P. aeruginosa. ( Forrest, A., et al., Pharmacokinetics and pharmacodynamics of oral grepafloxacin patients with acute bacterial exacerbations of chronic bronchitis, J. Antimicro. Chemother., 40, p. 45-57, 1997)

d. Human clinical trials A phase 1 human clinical trial was studying the maximum recommended starting dose for grepafloxacin antibiotics. (Contrera, J., et al., Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose, Reg. Tox. Pharm., 40(3) p. 185- 206, 2004)

e. Review Article Grepafloxacin was compared alongside of other flouroquinolone antibiotics to test the effectiveness against gram positive bacteria. (Blondeau, J., et al., Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms, Int. J. Antimicro. Agents, 14 (4) p. 45-50, 2000)

Antibiotic name Diseases treated m log P Herbimycin Cancer = 1.507

SMILES IUPAC MIC values NC(=O)O[C@H]1C(/C)=C/[C@H](C)[C@@ [(2R,3S,5S,6R,7S,8E,10R,11S,12E, N/A H](OC)[C@@H](OC)C[C@H](C)[C@@H](O 14E)-2,5,6,11-tetramethoxy- C)C\2=C\C(=O)\C=C(\NC(=O)C(\C)=C\C=C/ 3,7,9,15-tetramethyl-16,20,22- [C@@H]1OC)C/2=O trioxo-17-azabicyclo[16.3.1] docosa-8,12,14,18,21-pentaen- 10-yl] carbamate

Emp. Formula, Molar mass Antibiotic group Trade names C30H42N2O9 , 574.66 g/mol Benzoquinone ansamycin N/A

Dipole Moment (Debye) Molecular Volume Surface Area 3.54 Debye 590.40 Å3 604.62 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 125.024 Å2 70563-58-5 0.006 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 2 11

References and summary a. MOA : Herbimycin binds to the chaperone protein, Hsp90, and prevents it from regulating cell cycle, growth, and survival. (Duncan, Roger F. "Inhibition of Hsp90 function delays and impairs recovery from heat shock." FEBS Journal 272.20 (2005): 5244-5256.)

b. Source : Herbimycin is extracted from the fermented broth of the soil isolate Streptomyces hygroscopicus (strain No. AM-3672) (Omura, S. A. T. O. S. H. I., et al. "Herbimycin, a new antibiotic produced by a strain of Streptomyces." The Journal of antibiotics 32.4 (1979): 255-261.)

c. Cell line Test (MIC) : The effect of Herbimycin version A (Herbimycin A) is tested against growth and activity of the pp60c-src human colon tumor cell lines. Herbimycin proved to be 40% effective in inhibiting growth at the dose of 125ng/mL. (Garcia, R., et al. "Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines." Oncogene 6.11 (1991): 1983-1989)

d. Human clinical trials : N/A

e. Review Article : N/A

Antibiotic name: Diseases treated: m log P= Imipenem Infections in respiratory tract -0.863

SMILES: IUPAC: MIC values: O=C(O)/C1=C( \SCC/N=C/N)C[C@H]2N1C( (5R,6S)-6-[(1R)-1-hydroxyethyl]- Two isolates used and a control;TAL =O)[C@@H]2[C@H](O)C.O 3-({2- 2480 MIC value of imipenem 128 µg/ml, [(iminomethyl)amino]ethyl}thio) TAL 3636 MIC value of imipenem 128 -7-oxo-1-azabicyclo[3.2.0]hept- 128 µg/ml, the control MIC value of 2-ene-2-carboxylic acid imipenem 0.5 µg/ml

Emp. Formula, Molar mass: Antibiotic group: Trade names: C12H17N3O4S, 299.352 g/mol Carbapenems Primaxin

Dipole Moment (Debye)= Molecular Volume= Surface Area= 6.45 Debye 255.282 Å3 317.80 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 116.223 Å2 74431-23-5 0.025 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N): atoms): 3 6

References and summary a. MOA: Imipenem acts as an antimicrobial through the inhibition of cell wall synthesis of various gram-positive and gram-negative bacteria. This inhibition of cell wall synthesis in gram-negative bateria is attained by binding to pencillin binding proteins (PBPs). In E. coli and selected strains of P. aeruginosa, imipenem has shown to have the highest affinity to PBP-2, PBP-1a, and PBP-1b. This preferential binding to PBP-2 and PBP-1b results in the direct conversion of the individual cell to a spheroblast, which leads to rapid cell lysis and death without filament formation.( Hashizume, T. E. R. U. T. A. K. A., et al. "Studies on the mechanism of action of imipenem (N- formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli." The Journal of antibiotics 37.4 (1984): 394.) b. Source: Imipenem is derived from thienamycin, which is produced by the bacterium Streptomyces cattleya (Kahan, Frederick M., et al. "Thienamycin: development of imipenem-cilastatin." Journal of Antimicrobial Chemotherapy 12.suppl D (1983): 1-35.)

c. Cell line Test (MIC):In the susceptibility of imipenem resistance B.fragilis isolates, two different types of isolates were used. TAL 2480 was one of the isolate and the MIC value was 128µg/ml and for the second isolate TAL3636 the MIC value was 128µg/ml. They also used a control isolate. Control MICs are the median values for 350 B. fragilis clinical isolates. The MIC value was 0.5 µg/ml for imipenem in the control.( Cuchural, G. J., M. H. Malamy, and F. P. Tally. "Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis." Antimicrobial agents and chemotherapy 30.5 (1986): 645-648.) d. Human clinical trials:A human clinical trial was carried out on imipenem prophylaxis in acute pancreatitis. . Seventy-four patients with computed tomographic (CT) scans demonstrating necrotizing pancreatitis within 72 hours of onset were randomly assigned to two groups receiving no antibiotic treatment or 0.5 gram of prophylactic imipenem administered intravenously every eight hours for two weeks. (Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483.) e. Review Article: Hashizume, T. E. R. U. T. A. K. A., et al. "Studies on the mechanism of action of imipenem (N-formimidoylthienamycin) in vitro: binding to the penicillin-binding proteins (PBPs) in Escherichia coli and Pseudomonas aeruginosa, and inhibition of enzyme activities due to the PBPs in E. coli." The Journal of antibiotics 37.4 (1984): 394. Kahan, Frederick M., et al. "Thienamycin: development of imipenem-cilastatin." Journal of Antimicrobial Chemotherapy 12.suppl D (1983): 1-35. Cuchural, G. J., M. H. Malamy, and F. P. Tally. "Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis." Antimicrobial agents and chemotherapy 30.5 (1986): 645-648. Pederzoli, Paolo, et al. "A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem." Surgery, gynecology & obstetrics 176.5 (1993): 480-483. f.

Antibiotic name Diseases treated m log P kanamycin Anti-Bacterial Agents = -5.696

SMILES IUPAC MIC values C1[C@H]([C@@H]([C@H]([C@@H] 2-(aminomethyl)- 6-[4,6- 10μg/ml against M. smegmat1 ([C@H]1N)O[C@@H]2[C@@H]([C@H diamino-3- [4-amino-3,5- ] ([C@@H]([C@H](O2)CN)O)O)O)O)O dihydroxy-6-(hydroxymethyl) [C@@H]3[C@@H]([C@H]([C@@H]([ tetrahydropyran-2-yl]oxy- 2- C@H](O3)CO)O)N)O)N hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol

Emp. Formula, Molar mass Antibiotic group Trade names C18H36N4O11 ,484.499 g/mol Aminoglycosides Kanamycin A Kanamycin B

Dipole Moment (Debye) Molecular Volume Surface Area 2.71 Debye 431.18Å3 455.45 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 282.624 8063-07-8 0.00628 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 11 15

References and summary a. MOA Aminoglycosides like kanamycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes 2 b. Source Streptomyces kanamyceticus ATCC 12853 as well on kanamycin production Galactose was found to be the most suitable carbon source, though dextrin, soluble starch, and potato starch gave moderate yields. Sodium nitrate and glycine were adequate nitrogen sources for kanamycin production1

c. Cell line Test (MIC) 10 µg/mL against M. smegmati (. Hatsumi, T., Bin, C.,Yoshihiko,N.,Yasuo M.,Schin-Ichi, Y., Molecular Analysis of Kanamycin and Vinomycin Resistancein Mycobacterium Smegmatis br use of the conjugation system,j of microbiol, Vol. 179(15),pg. 4795-4801,Aug. 1997

d. Human clinical trials 584 patients enrolled in clinical trials. Phase 3(. Park,J W.,Park, S R., Nepal, K., Han, AR., Ben Y H.,Yoo, Y J.,Kim,E J.,Kim D.,Sohng, J K., Yoon,Y J.,Discovery of parallel pathways of kanamycin biosynthesis allows antibiotics manipulation,Nat Chem Biol,Vol. 7,pg.843-853,November 2011.

e. Review Article 1.Reza, F., Ashkan, P., BAHAR, T.,Todd,W.,Effects of kanamycin on the macromolecular composition of kanamycin sensitive Escherichia coli DH5α strain, J Microbiol and Immunol, UBC, Vol. 9,pg31-38 2. Park,J W.,Park, S R., Nepal, K., Han, AR., Ben Y H.,Yoo, Y J.,Kim,E J.,Kim D.,Sohng, J K., Yoon,Y J.,Discovery of parallel pathways of kanamycin biosynthesis allows antibiotics manipulation,Nat Chem Biol,Vol. 7,pg.843-853,November 2011. 3. Hatsumi, T., Bin, C.,Yoshihiko,N.,Yasuo M.,Schin-Ichi, Y., Molecular Analysis of Kanamycin and Vinomycin Resistancein Mycobacterium Smegmatis br use of the conjugation system,j of microbiol, Vol. 179(15),pg. 4795- 4801,Aug. 1997.

Antibiotic name Diseases treated Bacterial m log P Keflin Infection of Blood or Tissues = 0.566

SMILES IUPAC MIC values O=C2N1/C(=C( \CS[C@@H]1[C@@H]2NC( (6R,7R)-3-[(acetoxy)methyl]-8- 0.125 µg/mL when tested for Group A =O)Cc3sccc3)COC(=O)C)C(=O)O oxo-7-[(2-thienylacetyl)amino]- Streptococci from Epithelial Cells 5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H16N2O6S2, 396.44g/moll Cephalosporins Keflin, Cemastin, Coaxin, Seflin.

Dipole Moment (Debye) Molecular Volume Surface Area 4.13 debye 353.62 Å3 93.331 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 113.011 A2 153-61-7 0.012 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 8

References and summary a. MOA Keflin causes the inhibition of cell wall synthesis through affinity for penicillin binding proteins (Drug bank and target data base (Imming, P., Sinning C, Meyer, A., Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 5(10), p.821-34, 2006).

b. Source Synthetic source gotten from reactions of several pre-existing chemicals (National Center for Biotechnology Information. U.S National library of Medicine, 2013).

c. Cell line Test (MIC) A cell line test was carried out to test for Group A Streptococci from Epithelial Cells (0.125 µg/mL ) (Kaplan, E., Chhatwal, G., Rohde M., Reduced Ability of Penicillin to Eradicate Ingested Group A Streptococci from Epithelial Cells: Clinical and Pathogenetic Implications. Oxford Journals. 43(11) p. 1398-1406, 2006).

d. Human clinical trials A clinical trial was done to reveal the efficiency of cephalothin were 88 patients were given a short course of cephalothin. (Cameron, J., Imbembo, A., Kieffer, R., Spray, S., Baker, R., Prospective clinical trial of antibiotics for pulmonary resections. Surg Gynecol Obstet, 1981).

e. Review Article A review was carried out on the efficacy of antibiotics therapy on penetrating gunshot wondson 38 different cases. (Heiden, S., et al. Penetrating gunshot wounds of the cervical spine in civilians: Review of 38 cases. Journal of neurosurgery 42(5) p. 575-579, 1975).

Antibiotic name Diseases treated m log P Levofloxacin Respiratory, Urinary infections = -0.262

SMILES IUPAC MIC values C[C@H]1COc2c3n1cc(c(=O)c3cc(c2N4CCN (S)-9-fluoro-2,3-dihydro-3- 0.03 mg/L when tested for inhibition (CC4)C)F)C(=O)O methyl-10-(4-methylpiperazin-1- against Legionella pneumophila, yl)-7-oxo-7H-pyrido[1,2,3-de]- Mycoplasma pneumoniae and 1,4-benzoxazine-6-carboxylic Chlamydia pneumonia. acid

Emp. Formula, Molar mass Antibiotic group Trade names C18H20FN3O4, 361.368 g/mol Fluoroquinolones Levaquin, Tavanic

Dipole Moment (Debye) Molecular Volume Surface Area 5.3 Debye 341.80 Å3 342.41 Å3

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 75.014 Ų 100986-85-4 0.016 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 1 7

References and summary a. MOA The mechanism of action of levofloxacin is similar in most fluoroquinolones. Inhibition occurs from a bacterial Deoxyribonucleic acid Gyrase. (Davis, Rick, and Harriet M. Bryson. "Levofloxacin." Drugs 47.4 (1994): 677-700.

b. Source Levofloxacin, part of the Fluoroquinolone group, is an isomer of ofloxacin. It’s also a good antibacterial agent. (Langtry, Heather D., and Harriet M. Lamb. "Levofloxacin." Drugs 56.3 (1998): 487-515.

c. Cell line Test (MIC) A cell line test of 0.03 mg/L was carried out to test for inhibition against Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumonia. (Critchley, I. A., et al. "In vitro activity of levofloxacin against contemporary clinical isolates of Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North America and Europe." Clinical microbiology and infection 8.4 (2002): 214-221. d. Human clinical trials A human clinical trial was created to test the efficacy and safety of Levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in Human Skin Blister Fluid. (Trampuz, Andrej, et al. "Pharmacokinetics and pharmacodynamics of levofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in human skin blister fluid." Antimicrobial agents and chemotherapy 44.5 (2000): 1352-1355.

e. Review Article 1. Levofloxacin is very effective when it comes to the treatment of many bacterial infections. (Ball, Peter. "Efficacy and safety of levofloxacin in the context of other contemporary fluoroquinolones: a review." Current therapeutic research 64.9 (2003): 646-661.

2. When it comes to gram-positive aerobic organisms, Levofloxacin has an increased exertion. (Wimer, Steven M., Lori Schoonover, and Mark W. Garrison. "Levofloxacin: a therapeutic review." Clinical therapeutics 20.6 (1998): 1049-1070.

Antibiotic name Diseases treated m log P Lincomycin and Cellulitis = 0.826

SMILES O=C(N[C@@H]([C@H]1O[C@H](S IUPAC MIC values C)[C@H](O)[C@@H](O)[C@H]1O)[C@H]( (2S,4R)-N-[(1R,2R)-2-hydroxy-1- 64 mg/l against Brachyspira O)C)[C@H]2N(C)C[C@H](CCC)C2 [(2R,3R,4S,5R,6R)-3,4,5- hyodysenteriae trihydroxy-6- (methylsulfanyl)oxan-2-yl]propyl]- 1-methyl-4-propylpyrrolidine-2-

carboxamide

Emp. Formula, Molar mass Antibiotic group Trade names

406.538 g/mol, C18H34N2O6S Lincosamides Lincocin

Dipole Moment (Debye) Molecular Volume Surface Area 3 5.53 Debye 379.206 A 102.537 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 2 122.482 A 154-21-2 0.0539 Debye/ A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 8 5

References and summary a. MOA The mechanism of action for Lincomycin is inhibition of peptide bond formation. (Igarashi, Kazuei, Hideo Ishitsuka, and Akira Kaji. "Comparative studies on the mechanism of action of lincomycin, streptomycin, and erythromycin."Biochemical and biophysical research communications 37.3 (1969): 499-504.)

b. SourceLincomycin is comes from actinomyces Streptomyces lincolnensis and can be prepared from microorganism S. lincolnensis var. lincolnensis.( Bergy, Malcolm E., John H. Coats, and Vedpal S. Malik. "Process for preparing lincomycin." U.S. Patent No. 4,271,266. 2 Jun. 1981.)

c. Cell line Test (MIC)The MIC90 value of lincomycin against 76 field isolates of Brachyspira hyodysenteriae was 64 mg/l.( Karlsson, Märit, Sophy L. Oxberry, and David J. Hampson. "Antimicrobial susceptibility testing of Australian isolates of< i> Brachyspira hyodysenteriae using a new broth dilution method." Veterinary microbiology84.1 (2002): 123- 133.)

d. Human clinical trialsThere were human clinical trials conducted for lincomycin against anaerobic infections. (Bartlett, John G., Vera L. Sutter, and Sydney M. Finegold. "Treatment of anaerobic infections with lincomycin and clindamycin." New England Journal of Medicine 287.20 (1972): 1006-1010.)

e. Review Article (Reynolds, Mark A., et al. "The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review." Annals of periodontology 8.1 (2003): 227-265.) f. (Takafuji, Ernest T., et al. "An efficacy trial of doxycycline chemoprophylaxis against leptospirosis." New England Journal of Medicine 310.8 (1984): 497-500.)

Antibiotic name Diseases treated m log P Linezolid Pneumonia, Skin infections = 0.924

SMILES IUPAC MIC values O=C1O[C@@H](CNC(=O)C)CN1c3cc(F)c(N (S)-N- ({3-[3-fluoro-4-(morpholin- ≤2 μg/ml when tested for inhibition

2CCOCC2)cc3 4-yl)phenyl]-2-oxo-1,3- against Staphylococcus aureus

oxazolidin-5-

yl}methyl)acetamide

Emp. Formula, Molar mass Antibiotic group Trade names

C16H20FN3O4, 337.346 g/mol Oxazolidinones Zyvox, Zyvoxam, Zyvoxid

Dipole Moment (Debye) Molecular Volume Surface Area 3 3 6.3 Debye 322.95 Å 341.10 Å

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 71.113 Ų 165800-03-3 0.020 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 1 5

References and summary a. MOA The mechanism of action of Linezolid involves the disorder of messenger RNA. This interferes with the formation of bacteria and from this proteins are formed. (Shinabarger, Dean L., et al. "Mechanism of action of oxazolidinones: effects of linezolid and on translation reactions." Antimicrobial agents and chemotherapy 41.10 (1997): 2132-2136.

b. Source This is a molecular view to Linezolid and its resistance. (Kosowska-Shick, Klaudia, et al. "Molecular and epidemiologic characteristics of linezolid-resistant coagulase-negative staphylococci at a tertiary care hospital." Diagnostic microbiology and infectious disease 68.1 (2010): 34-39.

c. Cell line Test (MIC) A cell line test of ≤2 μg/ml was carried out to test for inhibition against Staphylococcus aureus. (Mendes, Rodrigo E., et al. "Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States." Antimicrobial agents and chemotherapy 58.2 (2014): 1243-1247.

d. Human clinical trials This clinical trial tested the treatment of complex skin infections caused by methicillin resistant Staphylocccus aureus (MRSA). It was tested using Linezolid and how it differ in different populations. ( Puzniak, Laura A., et al. "Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus : a pooled data analysis." Diagnostic microbiology and infectious disease (2013). e. Review Article This article is a review of the effectiveness of Linezolid on tuberculosis and other infections. (Cox, H., and N. Ford. "Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis [Review article]." The International Journal of Tuberculosis and Lung Disease 16.4 (2012): 447-454.

A review to compare success and failure rates in patients treated with linezolid. (Kalil, Andre C., et al. "Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis." BMJ open 3.10 (2013): e003912.

Antibiotic name Diseases treated m log P Lomefloxacin Bronchitis, Urinary tract infections = 0.081

SMILES IUPAC MIC values Fc1c(c(F)c2c(c1)C(=O)C( \C(=O)O)=C/N2CC (RS)-1-Ethyl-6,8-difluoro-7-(3- An MIC value of 0.12 μg/ml was found )N3CC(NCC3)C methylpiperazin-1-yl)-4-oxo- when testing against Legionella quinoline-3-carboxylic acid pneumophila

Emp. Formula, Molar mass Antibiotic group Trade names C17H19F2N3O3, 351.348 g/mol Quinolones Maxaquin, Okacyn, Uniquin

Dipole Moment (Debye) Molecular Volume Surface Area 3.74 debye 333.51 Å3 64.57 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 74.569 Å2 98079-51-7 0.011 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA This antibiotics inhiobits DNA gyrase by ensnaring the enzyme as a complex with the DNA substrate. (Palumbo, M., et al. On the mechanism of action of quinolone drugs. Trends in microbiology. (1)6, p. 232-235, 1993).

b. Source Lomefloxacins are synthetic antimicrobial agents. (National Center for Biotechnology Information, U.S. National Library of Medicine).

c. Cell line Test (MIC) An MIC value of 0.12 μg/ml was found when testing against Legionella pneumophila. (Dubois, J., et al. In vitro activity of lomefloxacin against isolates of Legionella species. Diagnostic microbiology and infectious disease. (12)3, p.89-91, 1989).

d. Human clinical trials In this study, lomefloxacin was tested against the treatment of chronic osteomyelitis. (Greenberg, N., et al. Ciprofloxacin, lomefloxacin, or levofloxacin as treatment for chronic osteomyelitis. Antimicrobial agents and chemotherapy. (44)1, p. 164-166, 2000).

e. Review Article This article is a review on quinolones activity against anaerobes. (Appelbaum, C., Quinolone activity against anaerobes. Drugs (58)2, p. 60-64, 1999).

Antibiotic name Diseases treated m log P Loracarbef Tonsilitis and streptococcal pharyngitis = -1.67

SMILES IUPAC MIC values Cl \C3=C(/C(=O)O)N2C(=O)[C@@H](NC(= (6R,7S)-7-[[(2S)-2-amino-2- 40 mg/L for strains of Listeria species O)[C@@H](c1ccccc1)N)[C@H]2CC3.O phenylacetyl]amino]-3-chloro-8- oxo-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names 349.769 g/mol, C16H16ClN3O4 Carbapenem (Some classify as a Lorabid 2nd generation Cephalosporin)

Dipole Moment (Debye) Molecular Volume Surface Area 3.14 Debye 288.842 A3 347.52 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume)0.0109 112.729 A2 76470-66-1 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 4 7

References and summary a. MOAThe mechanism of action for loracarbef is the inhibition of cell wall synthesis of various Gram-positive and Gram-negative bacteria. (Birnbaum, Jerome, et al. "Carbapenems, a new class of beta-lactam antibiotics: discovery and development of imipenem/cilastatin." The American journal of medicine 78.6 (1985): 3-21.)

b. Source Loracarbef is a synthetic "carba" analogue of cefaclor.( Kovach, Paul M., Ronald J. Lantz, and Gordon Brier. "High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine." Journal of chromatography B: Biomedical sciences and applications 567.1 (1991): 129-139.)

c. Cell line Test (MIC)The MIC value of loracarbef was approximately 40 mg/L for strains of Listeria species.( Troxler, R., et al. "Natural antibiotic susceptibility of Listeria species: L. grayi, L. innocua, L. ivanovii, L. monocytogenes, L. seeligeri and L. welshimeri strains." Clinical microbiology and infection 6.10 (2000): 525-535.)

d. Human clinical trialsHuman clinical trials were conducted to test the pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of cefprozil, loracarbef, and other drugs. (Schatz, Beth S., et al. "Comparison of cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and ceftibuten." The Annals of pharmacotherapy 30.3 (1996): 258- 268.)

e. Review Article(Force, R. W., and M. C. Nahata. "Loracarbef: a new orally administered antibiotic." The Annals of pharmacotherapy 27.3 (1993): 321-329.)

f. (Spiegel, Carol A., et al. "Anaerobic bacteria in nonspecific vaginitis." New England Journal of Medicine 303.11 (1980): 601-607.)

Antibiotic name Diseases treated m log P Mefoxin Skin, bone, urinary tract infections = 0.021

SMILES IUPAC MIC values

O=C2N1/C(=C(\CS[C@@H]1[C@]2(OC)NC (6S,7R)-4-(carbamoyloxymethyl)- The MIC values range from 1.2 to 50

(=O)Cc3sccc3)COC(=O)N)C(=O)O 7-methoxy- µg/mL when tested for Escherichia coli

8-oxo-7-[(2-thiophen-2-

ylacetyl)amino]-5-thia-

1-azabicyclo[4.2.0]oct-2-ene-2-

carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H17N3O7S2, 427.454 g/mol Mefoxin

Dipole Moment (Debye) Molecular Volume Surface Area 5.41 debye 371.03 Å3 128.235 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 148.268 Å2 35607-66-0 0.015 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 4 10

References and summary a. MOA Cefoxitin inhibits cell wall synthesis in bacteria particularly gram negative and gram positive bacteria. (Onishi, H., et al. Observations on the mode of action of cefoxitin. Annals of the New York Academy of Sciences (235)1, p. 406-425, 1974).

b. Source Cefoxitin are a semi-synthetic derivative of . (Wheeler, L., et al. High-performance liquid chromatographic assay for measurement of cefoxitin in serum. Journal of Chromatography B: Biomedical Sciences and Applications (183)3, p. 357-362, 1980).

c. Cell line Test (MIC) The MIC values range from 1.2 to 50 µg/mL when tested for Escherichia coli. (Slocombe, B., et al. BRL 17421, a novel beta-lactam antibiotic, highly resistant to beta-lactamases, giving high and prolonged serum levels in humans. Antimicrobial Agents and Chemotherapy (20)1, p. 38-46, 1981).

d. Human clinical trials A cefoxitin was tested on humans in comparison with other cephalosporin to determine the most efficient antibiotic against antimicrobial activity, human pharmacokinetics, and toxicology (Brumfitt, William, et al. Cefoxitin and cephalothin: antimicrobial activity, human pharmacokinetics, and toxicology. Antimicrobial agents and chemotherapy (6)3, p. 290-299, 1974).

e. Review Article Cefoxitin was reviewed along with other drugs on their efficacy in treatment of joint and bone infections. (Stott, N., Review article: paediatric bone and joint infection. Journal of Orthopaedic Surgery (9)1, 2001).

Antibiotic name Diseases treated m log P Meropenem Meningitis caused by Listeria = -0.851

SMILES IUPAC MIC values

O=C3N2\C(=C(\S[C@H]1C[C@@H] 3-[5-(dimethylcarbamoyl) 0.05 mg/L was active against

(C(=O)N(C)C)NC1)[C@H](C)[C@@ pyrrolidin-2-yl] sulfanyl-6- (1- L. monocyrogenes at pH 7.4

H]2[C@H]3[C@H](O)C)C(=O)O hydroxyethyl)-4-methyl-7-

oxo- 1-azabicyclo[3.2.0] hept- 0.04 to 0.08 mg/L was active against

2-ene-2-carboxylic acid S. aureus at pH 5.5

Emp. Formula, Molar mass Antibiotic group Trade names C17H25N3O5S Carbapenem Monan, Meronem 383.469 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3.25 Debye 370.37 Å3 393.89 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 93.340 Å2 119478-56-7 0.0088 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 7

References and summary a. MOA Meropenem works by inhibiting the cell wall synthesis of microbes. (Bourne, C.R., Wakeham, N., Bunce, R.A., Berlin.K.D , Barrow, W.W., Classifying compound mechanism of action for linking whole cell phenotypes to molecular targets, J. Mol. Recognit., 25(4), 216–223, 2012.)

b. Source Meropenem is a synthetic derivative of thienamycin, which is a natural product derived from Streptomyces cattleya (Criag, W.A., The Pharmacology of Meropenem, A New Carbapenem Antibiotic., Clin. Infect. Dis., 24(Supplemental 2), S266-S275, 1997.)

c. Cell line Test (MIC) 0.05 mg/L was active against L. monocyrogenes at pH 7.4 0.04 to 0.08 mg/L was active against S. aureus at pH 5.5 (Lemaire, S., Bambeke, F.V., Mingeot-Leclercq, M-P., Tulkens, P.M., Activity of three b-lactams (ertapenem, meropenem and ampicillin) against intraphagocytic Listeria monocytogenes and Staphylococcus aureus, J. Antimicrob. Chemother., 55(6), 897-904, 2005.)

d. Human clinical trials Meropenem is in Phase III of clinical trials for treating complicated intra-abdominal infection. (Lucasti, C., Jasovich, A., Umeh, O., Jiang, J., Kaniga, K., Friedland, I., Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra-abdominal infection: A phase III, prospective, multicenter, randomized, double-blind, noninferiority study, Clin. Thera., 30(5), 868-883, 2008.)

e. Review Article [1]. Zhanel, G.G., Wiebe, R., Dilay, L., Thomson, K., Rubinstein, E., Hoban, D.J., Noreddin, A.M., Karlowsky, J.A., Comparative review of the carbapenems, Drugs, 67(7), 1027-1052, 2007. [2]. Fish, D.N., Singletary, T.J., Meropenem, a New Carbapenem Antibiotic, Pharmocotherapy, 17(4), 644-669, 1997.

Antibiotic name Diseases treated m log P = 2.535 Metamide Uremia, malignancy, infection

SMILES IUPAC MIC values Clc1cc(c(OC)cc1N)C(=O)NCCN(CC)CC 4-amino-5-chloro-N-(2- Staphylocci: 0.5 µg/ml (diethylamino)ethyl)- 2-methoxybenzamide

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C14H22ClN3O2 Metoclopramide: antiemetic and Maxolon, Degan, Pulin Molar mass: 299.802 g/mol gastroprokinetic agent

Dipole Moment (Debye) Molecular Volume Surface Area 3.19 Debye 307.69 Å3 58.609 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 67.593 Å2 364-62-5 0.01 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 5 3

References and summary a. MOA It inhibirs the presynaptic D2 receptors. (Rao, AS., Camilleri, M., Metoclopramide and tardive dyskinesia, Aliment Pharmacol Ther., 31, 11-19, 2010). 2

b. Source Staphylococcus (Prados, AP., Kreil, V., Albarellos, G., Waxman, S., Rebuelto, M., Metoclopramide modifies oral cephalexin pharmacokinetics in dog., J Vet Med B., 30(2), 127-131. 2007). 1

c. Cell line Test (MIC) Staphylocci: 0.5 µg/ml (Prados, AP., Kreil, V., Albarellos, G., Waxman, S., Rebuelto, M., Metoclopramide modifies oral cephalexin pharmacokinetics in dog., J Vet Med B., 30(2), 127-131. 2007). 1

d. Human clinical trials Condition: Nausea, extrapyramidal symptoms. Intervention: Metoclopramide Phase: 4 Condition: Headache Intervention: Metoclopramide Phase: 4

e. Review Article 1) Prados, AP., Kreil, V., Albarellos, G., Waxman, S., Rebuelto, M., Metoclopramide modifies oral cephalexin pharmacokinetics in dog., J Vet Med B., 30(2), 127-131. 2007. 2) Rao, AS., Camilleri, M., Metoclopramide and tardive dyskinesia, Aliment Pharmacol Ther., 31, 11-19, 2010.

Antibiotic name: Diseases treated: m log P= Methicillin Skin and soft tissue infections 1.743

SMILES: IUPAC: MIC values: OC(=O)[C@@H]2N3C(=O)[C@@H](NC(=O (2S,5R,6R) -6-[(2,6- 0.125µg/ml->100µg/mL against

)c1c(OC)cccc1OC)[C@H]3SC2(C)C dimethoxybenzoyl)amino]-3,3- Staphylococcus aureus, 15.6µg/mL-

dimethyl-7-oxo-4-thia-1- >1000µg/mL against Methicillin resistant

azabicyclo[3.2.0]heptane-2- Staphylococcus aureus and 0.39µg/mL

carboxylic acid against Streptococcus pneumonia.

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C17H20N2O6S, 380.422 g/mol Penicillin Dimocillin

Dipole Moment (Debye)= Molecular Volume= Surface Area= 7.40 Debye 321.843 Å3 385.77 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 105.174 Å2 61-32-5 0.023 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N): atoms): 2 6

References and summary a. MOA: Mechanism of action of methicillin it acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross- linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptideused in peptidogylcan synthesis. (Gladwin M., Trattler B. Clinical Microbiology made ridiculously simple. 3rd edition. Miami: MedMaster, Inc.; 2004.)

b. Source: Since Methicillin is in penicillin group that means it is a certain species of Penicillium and is produced when growth of the fungus is inhibited by stress.( Graham Dutfield (30 July 2009). Intellectual property rights and the life science industries: past, present and future. World Scientific. pp. 140–. ISBN 978-981-283-227-6. Retrieved 18 November 2010.)

c. Cell line Test (MIC): MRSA exhibited low-level resistance to CHX and the QACs, with MICs of 1·5 to 3-fold (CHX), and 2 to 4-fold (QACs) higher than MSSA. However, the MIC values for MRSA ranged between 0·025 (the MIC of MSSA) and 1 μg/mL with triclosan, and between <5 (the MIC of MSSA) and 75 μg/mL with DPBI. (Suller, M. T. E., and A. D. Russell. "Antibiotic and biocide resistance in methicillin-resistant< i> staphylococcus aureus and vancomycin- resistant enterococcus." Journal of Hospital Infection 43.4 (1999): 281-291.) d. Human clinical trials: This clinical trial was carried out to determine if linezolid is superior to vancomycin in the treatment of nosocomial (acquired in the hospital) pneumonia due to Methicillin Resistant Staphylococcus Aureus (MRSA) in adult subjects. Subjects entered in to the study will have proven healthcare-associated methicillin-resistant Staphylococcus aureus pneumonia which will be treated with either linezolid or vancomycin.( Pletz, Mathias W., Olaf Burkhardt, and Tobias Welte. "Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia: linezolid or vancomycin?-Comparison of pharmacology and clinical efficacy." European journal of medical research 15.12 (2010): 507.) e. Review Article: Gladwin M., Trattler B. Clinical Microbiology made ridiculously simple. 3rd edition. Miami: MedMaster, Inc.; 2004. Graham Dutfield (30 July 2009). Intellectual property rights and the life science industries: past, present and future. World Scientific. pp. 140–. ISBN 978-981-283-227-6. Retrieved 18 November 2010. Suller, M. T. E., and A. D. Russell. "Antibiotic and biocide resistance in methicillin-resistant< i> staphylococcus aureus and vancomycin-resistant enterococcus." Journal of Hospital Infection 43.4 (1999): 281-291. Pletz, Mathias W., Olaf Burkhardt, and Tobias Welte. "Nosocomial methicillin-resistant Staphylococcus aureus (MRSA) pneumonia: linezolid or vancomycin?-Comparison of pharmacology and clinical efficacy." European journal of medical research 15.12 (2010): 507. f.

Antibiotic name Diseases treated m log P Metronidazole Treats anaerobic bacteria =-0.468

SMILES IUPAC MIC values CC1=NC=C(N1CCO)[N+](=O)[O -] 2-(2-Methyl-5-nitro-1H- 0.5 µg/ mol when tested on isolated imidazol-1-yl)ethanol strains of Clostridium difficile

Emp. Formula, Molar mass Antibiotic group Trade names C6H9N3O3 Antibiotic Anabact, and Acromona 171.2 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 5.47 Debye 160.74 Å3 61.713 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 83.878 Å2 443-48-1 0.0340 Debye / Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 1 6

References and summary a. MOA The mechanism of action is it inhibits the anaerobes in the metabolism, which ultimately effects the biochemical reaction. (Hirsh, Jack, et al. "Oral anticoagulants mechanism of action, clinical effectiveness, and optimal therapeutic range." CHEST Journal 108.4_Supplement (1995): 231S-246S.)

b. Source The source for Metronidazole is it is a synthetic drug. (Hui, Xu, et al. "Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines." Bioorganic & medicinal chemistry letters 16.4 (2006): 815-820.)

c. Cell line Test (MIC) The MIC value was 0.5 µg/mol when tested on isolated strains of Clostridium difficile. (Jang, S. S., et al. "Antimicrobial susceptibilities of equine isolates of Clostridium difficile and molecular characterization of metronidazole-resistant strains." Clinical infectious diseases 25.Supplement 2 (1997): S266-S267.)

d. Human clinical trials Penicillin and Metronidazole in Treatment of Peritonsillar Abscess. The purpose of the trial was to study whether broad spectrum antibiotics are required in addition to abscess drainage. This was done by giving some patients penicillin and some methonidazole and then the comparisons were analyzed. The trial has completed Phase 4.

e. Review Article METRONIDAZOLE TO PREVENT PRETERM DELIVERY IN PREGNANT WOMEN f. WITH ASYMPTOMATIC BACTERIAL VAGINOSIS.( Carey, J. Christopher, et al. "Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis." New England Journal of Medicine 342.8 (2000): 534-540.). The article is about whether metronidazole affects a women’s by altering the biochemical reactions.

Antibiotic name Diseases treated m log P Mezlocillin ascending cholangitis = 0.959

SMILES O=C(O)[C@@H]3N4C(=O)[C@@H](NC( IUPAC MIC values =O)[C@@H](c1ccccc1)NC(=O)N2C(=O)N(S(=O) (2S,5R,6R)-3,3-dimethyl-6- 0.06 mg/l for B. burgdorfer (=O)C)CC2)[C@H]4SC3(C)C [[(2R)-2-[(3-methylsulfonyl- 2-oxo-imidazolidine-1- carbonyl)amino]-2-phenyl-acetyl] amino]-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C21H25N5O8S2, 539.584 g/mol Penicillins Mezlin

Dipole Moment (Debye) Molecular Volume Surface Area 3 6.99 Debye 434.271 A 155.439 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 2 173.493 A 51481-65-3 0.04497 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 13

References and summary a. MOAThe mechanism of action for Mezlocillin is the inhibition of the third and last stage of bacterial cell wall synthesis. It does this by binding to penicillin binding proteins. (Tenover, Fred C. "Mechanisms of antimicrobial resistance in bacteria." The American journal of medicine 119.6 (2006): S3-S10.)

b. SourceMezlocillin is a synthetic drug. (König, H. B., et al. "[Mezlocillin: a penicillin from the acylureido series. Synthesis and chemical properties]." Arzneimittel-Forschung 33.1 (1982): 88-90.)

c. Cell line Test (MIC)Mezlocillin was tested against the in vitro susceptibility of B. burgdorfer with MIC90, ≤0.06 mg/l. (Hunfeld, K-P., et al. "In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, and fusidic acid against< i> Borrelia burgdorferi." International journal of antimicrobial agents 17.3 (2001): 203- 208.)l

d. Human clinical trialsMezlocillin was studied against human necrotizing pancreatitis. ( Bassi, C., et al. "Behavior of antibiotics during human necrotizing pancreatitis."Antimicrobial agents and chemotherapy 38.4 (1994): 830-836.)

e. Review Article(Henderson, J. L., R. E. Polk, and B. J. Kline. "In vitro inactivation of gentamicin, tobramycin, and netilmicin by carbenicillin, azlocillin, or mezlocillin." American Journal of Health-System Pharmacy 38.8 (1981): 1167-1170.) f. (Knothe, H. "[Antibacterial activity of mezlocillin and azlocillin/A survey (author's transl)]." Arzneimittel- Forschung 29.12a (1978): 1916-1920.)

Antibiotic name Diseases treated m log P Minocycline Acne vulgaris =-0.228

SMILES IUPAC MIC values

CN(C)[C@@H]1C(\O)=C(\C(N)=O)C(=O)[C (2E,4S,4aR,5aS,12aR)- 2-(amino- C. trachomatis MIC50 = 0.03 mg/L

@@]2(O)C(/O)=C3/C(=O)c4c(O)ccc(c4C[C hydroxy-methylidene)- 4,7- MIC90 = 0.03 mg/L

@H]3C[C@@H]12)N(C)C bis(dimethylamino)- 10,11,12a- C. pneumoniae MIC50 = 0.06 mg/L

trihydroxy-4a,5,5a,6- tetrahydro- MIC90 = 0.06 mg/L

4H-tetracene- 1,3,12-trione C. psittaci MIC50 = 0.03 mg/L

MIC90 = 0.06 mg/L

Emp. Formula, Molar mass Antibiotic group Trade names C23H27N3O7 , 457.477 g/mol Tetracycline Dynacin, Minocin, Monodox, Minomycin, Minoderm, Akamin

Dipole Moment (Debye) Molecular Volume Surface Area 6.19 Debye 431.15 Å3 431.14 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 130.937 Å2 10118-90-8 0.014 Deybe/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 6 10

References and summary a. MOA : Minocycline prevents protein syntheis by binding to the 30S ribosomal subunit. (Beliavskaia, I V, et al. "Study Of The Mechanism Of Action Of Minocycline And Of Certain Other Tetracycline Group Compounds." Antibiotiki 21.3 (1976): 242-245.)

b. Source : In this article minocycline is synthesiszed from9-nitro-6-demethyl-6-deoxytetracycline. (Church, Robert FR, Robert E. Schaub, and Martin J. Weiss. "Synthesis of 7-Dimethylamino-6-demethyl-6-deoxytetracycline (Minocycline) via 9-Nitro-6-demethyl-6-deoxytetracycline." The Journal of organic chemistry 36.5 (1971): 723- 725.)

c. Cell line Test (MIC) : The ability of minocycline to inhibit the protein synthesis of E2 and BV2 miroglial cells is examined. (Kim, Sung-Soo, et al. "Inhibitory action of minocycline on lipopolysaccharide-lnduced release of nitric oxide and prostaglandin E2 in BV2 microglial cells." Archives of pharmacal research 27.3 (2004): 314-318.)

d. Human clinical trials: In this trial minocycline was tested in combination with creatine as a treatment for patitents with early Parkinson’s disease. (NINDS NET-PD Investigators. "A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease." Neurology 66.5 (2006): 664-671.)

e. Review Article: This article summarizes literature and clinical trials that involve the use of minocycline as treatment. The article also compares the safety of minocycline use to that of doxycycline. (Kelly, Smith, and Leyden James J. "Review Article: Safety Of Doxycycline And Minocycline: A Systematic Review." Clinical Therapeutics 27.(n.d.): 1329-1342.)

Antibiotic name Diseases treated meningitis, m log P 0.394 Moxifloxacin tuberculosis, endocarditis

SMILES IUPAC 1-cyclopropyl-7-[(1S,6S)- MIC values COC1=C2C(=CC(=C1N3C[C@@H]4CCCN[C 2,8-diazabicyclo[4.3.0]non-8-yl]- S. pneumonia; 0.06–0.25 5 µg/mL @@H]4C3)F)C(=O)C(=CN2C5CC5)C(=O)O 6-fluoro-8-methoxy-4-oxo- quinoline-3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C21H24FN3O4, 401.431 g/mol Quinolone Avelox

Dipole Moment (Debye) Molecular Volume Surface Area 7.22 Debye 404.76 Å3 412.93 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 83.803 Å2 354812-41-2 0.018 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 2 7

References and summary a. MOA Moxifloxacin is a fourth generation fluoroquninolone antibiotic. It has a broad-spectrum of activity against both Gram-negative and Gram-positive bacteria. Moxifloxacin, and quinolones in general, function by inhibiting enzymes essential to DNA replication, in so doing it inhibits cell replication. (Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS,Sept, 377–392, 1997).

b. Source Moxifloxacin is a synthetic antibacterial agent from the quinolone family, specifically a subset known as fluoroquinolone, these are quinolone analogs that contain a fluorine atom. (Andersson, Monique I., Alasdair P. MacGowan. “Development of the quinolones”. Journal of Antimicrobial Chemotherapy 51, Suppl. S1, 1–11. 2003)

c. Cell line Test (MIC) Moxifloxacin was found to have excellent activity against a broad spectrum of bacteria; exhibiting MIC90 values of 0.06–0.25 5 µg/mL for Gram-negative, Gram-positive, anaerobic, and atypical bacterial strains. (Miravitlles, Marc. Moxifl oxacin in the management of exacerbations of chronic bronchitis and COPD. International Journal of COPD, 2(3) 191–204, 2007).

d. Human clinical trials A clinical study was carried out to assess the cardiac response of moxifloxacin vs levofloxacin in elderly patients with community acquired pneumonia. The study revealed no significant difference between the antibacterial agents and could not readily link any of the cardiac events to the use of these drugs. (Morganroth J, DiMarco JP, Anzueto A, Niederman MS, Choudhri S. A Randomized Trial Comparing The Cardiac Rhythm Safety Of Moxifloxacin Vs Levofloxacin In Elderly Patients Hospitalized With Community-Acquired Pneumonia. Chest. Vol. 128 No. 5, 3398-3406, 2005). e. Review Article (Samilski , Jennifer A. E., Tim T. Y. Lau, Dean H. T. Elbe, Amneet K. Aulakh, and Eric M. C. Lun. Drug Use Evaluation of Moxifloxacin (Avelox) Using a Hand-Held Electronic Device At a Canadian Teaching Hospital. P&T. Vol. 37 No. 5, 291-299, 2012).

Antibiotic name Diseases treated m log P Mupirocin Skin infections (impetigo), MRSA = 3.525

SMILES IUPAC MIC values O=C(O)CCCCCCCCOC(=O) \C=C(/C)C[C@@ 9-[(E)-4-[(2S,3R,4R,5S)-3,4- Staphylococcus aureus 8-256 mg/L H]2OC[C@H](C[C@@H]1O[C@H]1[C@@ dihydroxy-5-[[(2S,3S)-3- [(2S,3S)- Methicillin-resistant Staphylococcus H](C)[C@@H](O)C)[C@@H](O)[C@H]2O 3-hydroxybutan-2-yl]oxiran-2- aureus (MRSA) > 256 mg/L yl]methyl] oxan-2-yl]-3 methylbut-2-enoyl]oxynonanoic acid

Emp. Formula, Molar mass Antibiotic group Trade names C26H44O9 , 500.622 g/mol Monoxycarbolic acid Bactroban, Bactroban Nasal, Centany

Dipole Moment (Debye) Molecular Volume Surface Area 5.71 Debye 473.93 Å3 524.52 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 129.425 Å2 12650-69-0 0.012 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 17 available, attached to O, S, N) atoms) 4 9

References and summary a. MOA : Mupirocin is an effective antibiotic by preventing the formation of isoleucyl-tRNA by binding to the isoleucyl-tRNA synthetase enzyme. As a result, RNA synthesis and bacterial protein production is inhibited. (Hughes J, Mellows G: On the mode of action of pseudomonic acid: inhibition of protein synthesis in Staphylococcus aureus. J Antibiot (Tokyo). 1978 Apr;31(4):330-5.)

b. Source: Mupirocin is produced from the soil bacterium Pseudomonas fluorescens. (Thomas, Christopher M, et al. "Resistance To And Synthesis Of The Antibiotic Mupirocin." Nature Reviews. Microbiology 8.4 (2010): 281-289.)

c. Cell line Test (MIC) : In this cell line test mupirocin was evaluated against 14 strains of Staphylococcus aureus that have demonstrated resistance to mupirocin. As a result of the 18 month study, all four methicillin-susceptible S. aureus (MSSA) strains, the MIC values ranged from 3.1- 62.5 µg/mL. Of the 10 methicillin-resistant S. aureus (MRSA) strains, 8 ranged from 6.2- 50 µg/mL, while the remaining 2 strains exhibited high mupirocin resistance and had a MIC of > 5, 000 µg/mL. (Janssen, D. A., et al. "Detection and characterization of mupirocin resistance in Staphylococcus aureus." Antimicrobial agents and chemotherapy 37.9 (1993): 2003-2006.) d. Human clinical trials : Mupirocin is evaluated as treatment for Staphylococcus aureus of the nasal carriage. The 76 patients in that participated in the study were positive for human immunodeficiency virus (HIV). Five weeks of treatment with mupirocin twice daily proved to be suffient to eliminate the nasal S. aureus for several weeks; intermittent dosing was suggested for long-term elimination of the infection. (Martin, Jeffrey N., et al. "A randomized clinical trial of mupirocin in the eradication of Staphylococcus aureus nasal carriage in human immunodeficiency virus disease." Journal of Infectious Diseases 180.3 (1999): 896-899.) e. Review Article : This article reviews the effectiveness of mupirocin as treatment for patients and healthcare personnel with methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). (D.J., Hetem, and Bonten M.J.M. "Review: Clinical Relevance Of Mupirocin Resistance In Staphylococcus Aureus." Journal Of Hospital Infection 85.(n.d.): 249-256.)

Antibiotic name: Diseases treated: m log P= Nadifloxacin Acne Vulgaris -0.488

SMILES: IUPAC: MIC values: CC1CCC2=C3N1C=C(C(=O)C3=CC(=C2N4C (RS)-9 -Fluoro-8-(4-hydroxy- 0.1 µg/ml for S. aureus, 0.18 µg/ml for

CC(CC4)O)F)C(=O)O piperidin-1-yl)-5-methyl-1-oxo- Streptococcus Spp and CNS and 0.39

6,7-dihydro-1H,5H-pyrido[3,2,1- µg/ml for Propionibacterium Spp.

ij]quinoline-2-carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names:

C19H21FN2O4 , 360.385 g/mol Quinolone Acuatim, Nadoxin, Nadixa

Dipole Moment (Debye)= Molecular Volume= Surface Area= 5.93 Debye 314.464 Å3 357.17 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 82.77 Å2 124858-35-1 0.0189 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N): atoms): 2 7

References and summary a. MOA: Mechanism action of Nadifloxacin is to inhibit the enzyme DNA gyrase that is involved in bacterial DNA synthesis and replication and act directly as antioxidants against infiltrated neutrophils. (Akamatsu, H., et al. "Effect of nadifloxacin on neutrophil functions." The Journal of international medical research 23.1 (1994): 19-26.)

b. Source: Nadifloxacin is a synthetic bactericidal fluroquinolone. (Inoue, Yutaka, et al. "Comparison of the properties of brand-name and generic nadifloxacin creams." Medicina (Kaunas) 47.11 (2011): 616-22.)

c. Cell line Test (MIC): The MIC value for nadifloxacin againstn S. aureus was 0.1 µg/ml, 0.18 µg/ml for Streptococcus Spp and CNS and 0.39 µg/ml for Propionibacterium Spp. (Nenoff, P., U-F. Haustein, and N. Hittel. "Activity of nadifloxacin (OPC- 7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections." Chemotherapy 50.4 (2004): 196-201.)

d. Human clinical trials: Human clinical trials and studies have been carried out to see the efficiency of nadifloxacin in treating acne vullgaris. Nadifloxacin have also demonstrated activity against a broad range of gram-positive like staphylococcus aureus, methicillin- resistant S. aureus and staphylococcus epidermidis and gram-negative like pseudomonas aeruginose bacteria. ( Nenoff, Pietro. "Acne vulgaris and bacterial skin infections: review of the topical quinolone nadifloxacin." (2006): 643-654.)

e. Review Article: Akamatsu, H., et al. "Effect of nadifloxacin on neutrophil functions." The Journal of international medical research 23.1 (1994): 19-26. Inoue, Yutaka, et al. "Comparison of the properties of brand-name and generic nadifloxacin creams." Medicina (Kaunas) 47.11 (2011): 616-22. Nenoff, P., U-F. Haustein, and N. Hittel. "Activity of nadifloxacin (OPC-7251) and seven other antimicrobial agents against aerobic and anaerobic Gram-positive bacteria isolated from bacterial skin infections." Chemotherapy 50.4 (2004): 196-201. Nenoff, Pietro. "Acne vulgaris and bacterial skin infections: review of the topical quinolone nadifloxacin." (2006): 643- 654. f.

Antibiotic name Diseases treated m log P Nafcillin pneumonia, meningitis =3.269

SMILES IUPAC MIC values O=C(O)[C@@H]3N4C(=O)[C@@H](NC(=O (2S,5R,6R)-6-[(2-ethoxy-1- ≤ 0.4µg/ml when tested against )c2c1ccccc1ccc2OCC)[C@H]4SC3(C)C naphthoyl)amino]-3,3-dimethyl- Staphylococcus aureus. 7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C21H22N2O5S, 414.476 g/mol Penicillins Nafcill, Nallpen, Unipen

Dipole Moment (Debye) Molecular Volume Surface Area 2.33 Debye 400.25 Å3 83.84 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 95.94 Å2 985-16-0 0.006 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 2 7

References and summary a. MOA Nafcillin inhibits the biosynthesis of the bacterial cell wall. (Williamson, et. al. In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. (18)4, p. 629-37, 1980).

b. Source Nafcillin is a semi-synthetic antibiotic produced from several synthesis reactions. (Lipsky, A., et al. Daptomycin for treating infected diabetic foot ulcers: evidence from a randomized, controlled trial comparing daptomycin with vancomycin or semi-synthetic penicillins for complicated skin and skin-structure infections. Journal of Antimicrobial Chemotherapy (55)2, p. 240-245, 2005).

c. Cell line Test (MIC) ≤ 0.4µg/ml when tested against Staphylococcus aureus. (Sabath, L., et al. Susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to 65 antibiotics. Antimicrobial agents and chemotherapy (9)6, p. 962-969, 1976).

d. Human clinical trials A study was carried out on nafcillin to determine its efficiacy on bacterial Infections. (Smith, C., et al. Cefotaxime compared with nafcillin plus tobramycin for serious bacterial infections. A randomized, double-blind trial. Annals of internal medicine (101)4, p. 469-477, 1984).

e. Review Article A review on the literature on the interaction between warfarin and nafcillin was carried out to test the most effective treatment. (Kim, Y., et al. Interaction between warfarin and nafcillin: case report and review of the literature. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy (27)10, p.1467-1470, 2007).

Antibiotic name Diseases treated m log P Nalidixic acid Urinary tract infections, =0.813

SMILES IUPAC MIC values O=C \2c1c(nc(cc1)C)N(/C=C/2C(=O)O)CC 1-Ethyl-7-methyl-4-oxo- 0.25-4 μg/ml, Salmonella enterica var. [1,8]naphthyridine-3-carboxylic Typhi acid

Emp. Formula, Molar mass Antibiotic group Trade names C12H12N2O3, 232.239g/moll Quinolone NegGram

Dipole Moment (Debye) Molecular Volume Surface Area 5.10 Debye 230.62 Å3 253.63 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 72.196 Å2 389-08-2 0.022 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 1 5

References and summary a. MOA The mechanism of action was determined to be reversibly and selectively blocksing DNA replication in susceptible bacteria. Nalidixic acid inhibits a subunit of DNA gyrase and topoisomerase IV. (Goss, W., et al, Nalidixic acid-mode of action, Anti., 3 p. 174-196, 1975)

b. Source Nalidixic acid is a synthetic quinolone discovered in 1962. (Goss, W., et al, Nalidixic acid-mode of action, Anti., 3 p. 174-196, 1975)

c. Cell line Test (MIC) 0.25-4 μg/ml, Salmonella enterica var. Typhi (Ray, P., et al, Predictive efficacy of nalidixic acid resistance as a marker of fluoroquinolone resistance in Salmonella enterica var Typhi, J. Med. Res, 124, p. 105-108, 2006)

d. Human clinical trials Some properties of quinolones, including Nalidixic acid were determined using human volunteers in a safely conducted study where the drug was given orally in small dosages. (Hooper, D., et al, The Flouroquinolines: Pharmacology, Clinical Uses, and Toxicities in Humans, Antimicro. Chemother., 28(5) p. 716-721, 1985)

e. Review Article In several in vitro studies nalidixic acid was determined to be an effective drug when orally administrated. (Schaad, U., et al, Nalidixic acid in children: Retrospective matched study for cartilage toxicity, Infec., 15(3) p. 165- 168, 1987)

Antibiotic name Diseases treated m log P Neomycin Chemotherapeutic = -6.107

SMILES IUPAC MIC values O([C@H]3[C@H](O[C@@H]2O[C@ (2RS,3S,4S,5R)-5-amino-2- Neomycin was active against: (aminomethyl)-6-((2R,3S,4R,5S)-5- H](CO)[C@@H](O[C@H]1O[C@@ ((1R,2R,5R,6R)-3,5-diamino-2- M. Tuberculosis < 0.5 µg/ml, H](CN)[C@@H](O)[C@H](O)[C@H ((2R,3S,4R,5S)-3-amino-6- Hemophilus influenza 1.25 -2.5 ]1N)[C@H]2O)[C@@H](O)[C@H]( (aminomethyl)-4,5-dihydroxytetrahydro- µg/ml, 2H-pyran-2-yloxy)-6- N)C[C@@H]3N)[C@H]4O[C@@H]( hydroxycyclohexyloxy)-4-hydroxy-2- Staphylococcus aureus 0.156-0.625 [C@@H](O)[C@H](O)[C@H]4N)CN (hydroxymethyl)tetrahydrofuran-3- µg/ml yloxy)tetrahydro-2H-pyran-3,4-diol Emp. Formula, Molar mass Antibiotic group Trade names C23H46N6O13 Aminoglycoside Mycifradin, Fradiomycin, Neomin, 614.650 g/mol Neolate, and Neomas

Dipole Moment (Debye) Molecular Volume Surface Area 2.60 Debye 558.67 Å3 597.29 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 310.930 Å2 1404-04-2 0.00465 (Debye/Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 19 19

References and summary a. MOA Neomycin interferes with the formation of translation ignition apparatus by binding irreversibly to the 30S ribosomal subunit and 16S rRNA. (Wang, L., Wasserman, M.R., Feldman, M.B., Altman, R.B., Blanchard, S.C., mechanistic Insight Into Antibiotic Action on the Ribosome through single-molecule fluorescence imaging, Ann. N Y Acad. Sci., 1241(1), doi: 10.1111/j.1749-6632.2012.06839.x, 2011.) b. Source Neomycin was isolated from Streptomyces fradiae (Leach, B. E., DeVries, W. H., Nelson, H. A., Jackson, W. G., Evans, J. S., The Isolation and Characterization of Neomycin, J. Am. Chem. Soc., 73(6), 2797-2800, 1951.)

c. Cell line Test (MIC) Neomycin has been shown to be active against M. Tuberculosis < 0.5 µg/ml, Hemophilus influenza = 1.25 - 2.5 µg/ml and Staphylococcus aureus = 0.156-0.625 µg/ml (Waksman, S.A., Lechevalier, H.A., Harris, D.A., Neomycin-Production And Antibiotics Properties, J. Clin. Invest., 28, 934–939, 1949.)

d. Human clinical trials Neomycin was in Phase III (Double-Blind) of clinical trials to compare Neomycin and placebo in the treatment of exogenous hepatic encephalopathy. (Strauss, E., Tramote, R., Silva, E.P., Caly, W.R., Honain, N.Z., Maffei, R.A., de Sa, M.F., Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy, Hapato. Gastroentol., 39(6), 542-545, 1992.)

e. Review Article [1] Waksman, S.A, Lechevalier H.A., Neomycin, a New Antibiotic Active against Streptomycin-Resistant Bacteria, including Tuberculosis Organisms, Science, 109 (2830), 305–307, 1949. [2] Robertson, J.H., Baas, R., Yeager, R.L., Tsuji, K., Antimicrobial Activity of Neomycin C against Staphylococcus epidermidis, Appl. Microbiol., 22(6), 1164-1165, 1971.

Antibiotic name Diseases treated Bacterial m log P Netilmicin infections (Gentamicin resistant) = -3.703

SMILES IUPAC (2R,3R,4R,5R)-2- MIC values O[C@]3(C)[C@H](NC)[C@@H](O)[ {[(1S,2S,3R,4S,6R)-4-amino-3- 0.125-8 µg/ml, varies depending on C@@H](O[C@H]2[C@H](NCC)C[C {[(2S,3R)-3-amino-6- the microorganism (aminomethyl)-3,4-dihydro-2H- @H](N)[C@@H](OC1O\C (=C/CC1N)CN)[C@@H]2O)OC3 pyran-2-yl]oxy}-6-(ethylamino)- 2-hydroxycyclohexyl]oxy}-5- methyl-4-(methylamino)oxane- 3,5-diol

Emp. Formula, Molar mass Antibiotic group Trade names

C H N O , 475.587 g/mol Aminoglycoside Netromycin 21 41 5 7

Dipole Moment (Debye) Molecular Volume Surface Area 2.90 Debyes 473.82 Å3 509.22 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 173.673 Å2 56391-56-1 0.00612 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 11 12

References and summary a. MOA Interferes with transcription and translation process, by causing premature termination and inhibiting ribosomal translocation.(Kotra, L., Haddad, J., and Mobashery, S. Aminoglycosides: Perspectives on Mechanisms of Action and Resistance and Strategies to Counter Resistance, Antimicrobial Agents and Chemotherapy, Vol 44, No. 12, p. 3249, 2000)

b. Source Aminoglycosides that end in the suffix –micin are derived from the bacteria spp. (Crameri, R., and Davies, J. Increased Production of Aminoglycosides Associated with Amplified Antibiotic Resistance Genes, The Journal of Antibiotics, Vol 39, No. 1, p. 128, 1985)

c. Cell line Test (MIC) The concentrations will vary, because of the different microorganisms treated, 0.125- 8 µg/ml. (Miller, G.,et al, Biological Activity of Netilmicin, a Broad-spectrum Semisynthetic Aminoglycoside Antibiotic, Antimicrobial Agents and Chemotherapy, Vol. 10, No. 5, p. 829, 1976)

d. Human clinical trials Netilmicin was used as initial empirical therapy for febrile neutroenic patients. (Rozdzinski, E., et al, Once-daily versus thrice-daily dosing of netilmicin in combination with β- lactam antibiotics as empirical therapy for febrile neutropenic patients, Journal of Antimicrobial Chemotherapy, Vol. 31, No. 4, p. 585-589, 1993)

e. Review Article Netilmicin was tested on laboratory animals in order to determine the toxicity. (Luft, F., Netilmicin: a review of toxicity in laboratory animals, The Journal Of International Medical Research, Vol. 6, No. 4, p. 268-299, 1978)

Antibiotic name Diseases treated Uncomplicated m log P Nitrofurantoin urinary tract Infection = -0.05

SMILES IUPAC MIC values O=[N+]([O ])c2oc(/C=N/N1C(=O)NC( (E)-1-[(5-nitro-2- 32 µg/mL nitrofurantoin inhibits the

=O)C)cc2 furyl)methylideneamino]imida growth of E. faecium.

zolidine-2,4-dione

Emp. Formula, Molar mass Antibiotic group Trade names C8H6N4O5 Nitrofuran Derivatives Macrodantin, Furadantin, Macrobid 238.157 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3.99 Debye 202.16 Å3 235.87 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 100.634 Å2 67-20-9 0.0197 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 1 6

References and summary a. MOA Nitrofurantoin inhibits the protein synthesis by interfering with the bacterial ribosomal assembly. (McOsker, C. C., Fitzpatrick, P. M., Nitrofurantoin: Mechanism of action and implications for resistance development in common uropathogens, J. Antimicrob. Chemother., 33(suppl A), 23-30, 1994.)

b. Source Nitrofurantoin is synthetically derived from a nitrofuran compound. (Dodd, M. C., Stillman, W. B., The in vitro bacteriostatic action of some simple furan derivatives., J. Pharmacol. Exp. Ther. 82, 11-18, 1944.)

c. Cell line Test (MIC) 32 µg/mL of nitrofurantoin has been shown to inhibit the growth of E. faecium. Also, only 8 µg/mL of nitrofurantoin is required to prevent the growth of E. faecalis. (Zhanel, G. G., Hoban, D. J., Karlowsky, J. A., Nitrofurantoin Is Active against Vancomycin-Resistant Enterococci, Antimicrob. Agents Chemother., 45(1), 324-326, 2001.) d. Human clinical trials A total of 338 women participated in a randomized study to determine the cure rates with a 5 day course of nitrofurantoin versus a 3 day course of trimethoprim-sulfamethoxazone in treating an acute uncomplicated cystitis in women. Cure rate for nitrofurantoin treated group of patients was 84% and 79% for the trimethoprim-sulfamethoxazole treated group of patients. (Gupta, K., Hooton, T. M., Roberts, P. L., Stamm, W. E., Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women., Arch. Intern. Med., 167(20), 2207-2212, 2007.)

e. Review Article [1]. McCalla, D. R., Nitrofurans, In F. E. Hahn (ed.), Mechanism of action of antibacterial agents. Springer-Verlag, Berlin, Germany, p. 176-213, 1979. [2].Gleckman, R., Alvarez, S., Joubert, D. W., Drug therapy reviews: nitrofurantoin., Am. J. Heath-Syst. Ph., 36(3), 342-351, 1979.

Antibiotic name Diseases treated m log P Treats urinary tract infections =-0.691

SMILES IUPAC MIC values CCN1C=C(C(O)=O)C(=O)C2=CC(F) 1-ethyl-6-fluoro-4-oxo-7- < 4 µg/mL when tested on the =C(C=C12)N1CCNCC1 piperazin-1-yl-1H-quinoline- bacteria’s Enterobacteriaceae, 3-carboxylic acid Acinetobacter spp.,and Pseudomonas aeruginosa

Emp. Formula, Molar mass Antibiotic group Trade names C16H18FN3O3, 319.336 Fluoroquinolone Noroxin

Dipole Moment (Debye) Molecular Volume Surface Area 4.85 Debye 309.88 Å3 329.16 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 74.569 Å2 70458-96-7 0.0157 Debye/ Å2

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA The mechanism of action for this drug is inhibiting the DNA synthesis. (Newman, David J., Gordon M. Cragg, and Kenneth M. Snader. "Natural products as sources of new drugs over the period 1981- 2002." Journal of natural products 66.7 (2003): 1022-1037)

b. Source This drug has no natural source because it is made synthetically.( Newman, David J., Gordon M. Cragg, and Kenneth M. Snader. "Natural products as sources of new drugs over the period 1981- 2002." Journal of natural products 66.7 (2003): 1022-1037)

c. Cell line Test (MIC) The MIC value is < 4 µg/mL when tested on the bacteria’s Enterobacteriaceae, Acinteobacter, spp.,and Pseudomonas aeruginosa.( Barry, A. L., et al. "Antibacterial activities of ciprofloxacin, norfloxacin, oxolinic acid, , and nalidixic acid." Antimicrobial agents and chemotherapy 25.5 (1984): Page 633-334.)The study was done to see which quinolone drug is more effective against common )

d. Human clinical trials Norfloxacin In The Primary Prophylaxis Of Spontaneous Bacterial Peritonitis. The purpose of this trial was to test if oral administration of the drug would prevent an increase in the rate of spontaneous bacterial peritonitis fluid, and prevent the development of hepatorenal syndrome. The trial has completed after finishing phase 4

e. Review ArticleFluoroquinolone-Associated Tendinopathy: A Critical Review of the Literature (Khaliq, Yasmin, and George G. Zhanel. "Fluoroquinolone-associated tendinopathy: a critical review of the literature." Clinical infectious diseases 36.11 (2003): 1404-1410). The article is about various fluoroquinolone antimicrobials, and the parts of the body they treat

Antibiotic name Diseases treated treatment of m log P Ofloxacin pulmonary tuberculosis = -0.262

SMILES IUPAC MIC values Fc4cc1c2N(/C=C( \C1=O)C(=O)O)C(COc (RS)-7-fluoro-2-methyl-6-(4- 1. The conc. Of ofloxacin was 0.5 µg/ml 2c4N3CCN(C)CC3)C methylpiperazin-1-yl)-10-oxo-4- against Staphylococcus aureus and S. oxa-1- epidermidis azatricyclo[7.3.1.05,13]trideca- 2. 2 µg/ml against Streptococcus 5(13),6,8,11-tetraene-11- pneumonia carboxylic acid 3.4 µg/ml for Pseudomonas aeruginosa

Emp. Formula, Molar mass Antibiotic group Trade names C18H20FN3O4, 361.368 g/mol fluoroquinolone group of Floxin antibitic

Dipole Moment (Debye) Molecular Volume Surface Area 5.85 Debye 341.84 Å3 354.14 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 71.391 Å2 82419-36-1 0.0171 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 1 7

References and summary a. MOAinhibits DNA supercoiling activity of DNA gyrase in bacterial cell.( Sato, K., et al. Antibacterial activity of ofloxacin and its mode of action, Infect.,Vol 14(4),pg.226-230,1986

b. Source most abundant antibiotics found from untreated wastewater(Zuccato E., Castiglioni S., Bagnati R., Melis M., Fanelli R., Source, occurrence and fate of antibiotics in the Italian aquatic environment, J Hazard Mater, Vol.179(1- 3):1042-1048,July 15 2010.

c. Cell line Test (MIC) The MIC against 90% of all bacterial strains tested (MIC90) of ofloxacin was 0.5 µg/ml for Staphylococcus aureus and S. epidermidis, 2 µg/ml for Streptococcus pneumoniae, and 4 µg/ml for Pseudomonas aeruginosa.( Osato, M.S., Jensen, H.G., Trousdale, M.D., Bosso, J.A., Borrmann, L.R., Frank, J., Akers, P., The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates, Am . J Ophthamol, Vol. 108(4)pg.380-386,1989 d. Human clinical trials Ofloxacin was was given to 19 patients with chronic cavitary lung tuberculosis as single doses of 300 mg daily for 6 to 8 months(. Tsukamura M., Nakamura E., Yoshii S., Amano H., Therapeutic effect of a new antibacterial substance ofloxacin (DL8280) on pulmonary tuberculosis, The Am. Rev. of Resp. Dis.,Vol. 131(3),pg.352-356,1985.

e. Review Article 1. Osato, M.S., Jensen, H.G., Trousdale, M.D., Bosso, J.A., Borrmann, L.R., Frank, J., Akers, P., The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates, Am . J Ophthamol, Vol. 108(4)pg.380-386 2. Kresken,M., Wiedemann,B., Development of resistance to nalidixic acid and the fluoroquinolones after the introduction of norfloxacin and ofloxacin, Antimicrob. Agents Chemother., vol. 32(8)pg.1285-1288,August 1988.

Antibiotic name: Diseases treated: resistant m log P= Oxacillin staphylococci infections 2.1

SMILES: IUPAC : MIC values: Cc1c(c(no1)c2ccccc2)/C(=N/[C@H]3[C@ (2S,5R,6R)-3,3-dimethyl-6-[(5- 0.19-1.5 µg/ml MICs value of Oxacillin @H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O)/ methyl-3-phenyl- O 1,2-oxazole-4-carbonyl)amino]- 7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass: Antibiotic group: Trade names: C19H19N3O5S, 401.444 g/mol Penicillins Bactocill

Dipole Moment (Debye)= Molecular Volume= Surface Area:= 4.11 Debye 336.025 Å3 395.69 Å2

Surface Area (TPSA): CAS Number: D/V (dipoe moment/volume)= 116.232 Å2 66-79-5 0.0122 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N): atoms): 2 5

References and summary a. MOA: The Mechanism of Action of Oxacillin is that it binds the third and last stage of bacterial cell wall synthesis, By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall.( Williamson, R., R. Hakenbeck, and A. Tomasz. "In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae." Antimicrobial agents and chemotherapy 18.4 (1980): 629-637.)

b. Source: Oxacillin is semisynthetic penicillin derived from the penicillin nucleus, 6-aminopenicillanic acid.( Buddenbaum, Harry C., and Robert L. Robison. "Pharmaceutical compositions for storage in plastic containers and process therefor." U.S. Patent No. 4,533,542. 6 Aug. 1985.)

c. Cell line Test (MIC): A rapid detection of Non-multidrug-resistant and multidrug –resistant methicillin-resistant staphylococcus aureus using cycling probe technology for the mecA. A total of 90 clinical staphylococcus aureus isolates were tested and 30 methicillin- susceptible staphylococcus aureus with Oxacillin MIC values were between 0.19-1.5 µg/ml.( Merlino, J., B. Rose, and C. Harbour. "Rapid detection of non-multidrug-resistant and multidrug-resistant methicillin-resistant Staphylococcus aureus using cycling probe technology for the mecA gene." European Journal of Clinical Microbiology & Infectious Diseases 22.5 (2003): 322-323.) d. Human clinical trials:The objective of this clinical trial was to To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).( Ribeiro, Cristiane Franco, Giesela Fleisher Ferrari, and José Roberto Fioretto. "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study." Revista Panamericana de Salud Pública 29.6 (2011): 444-450.)

e. Review Article: Williamson, R., R. Hakenbeck, and A. Tomasz. "In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae." Antimicrobial agents and chemotherapy 18.4 (1980): 629-637. Buddenbaum, Harry C., and Robert L. Robison. "Pharmaceutical compositions for storage in plastic containers and process therefor." U.S. Patent No. 4,533,542. 6 Aug. 1985. Merlino, J., B. Rose, and C. Harbour. "Rapid detection of non-multidrug-resistant and multidrug-resistant methicillin- resistant Staphylococcus aureus using cycling probe technology for the mecA gene." European Journal of Clinical Microbiology & Infectious Diseases 22.5 (2003): 322-323. Ribeiro, Cristiane Franco, Giesela Fleisher Ferrari, and José Roberto Fioretto. "Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study." Revista Panamericana de Salud Pública 29.6 (2011): 444-450. f.

Antibiotic name Diseases treated m log P Oxolinic Acid Fish bacterial infections = 0.682

SMILES IUPAC MIC values CCN1C=C(C(=O)C2=CC3=C(C=C21)OCO3)C 5-Ethyl -8-oxo-5,8- 0.5 μg/mL when tested for inhibition

(=O)O dihydro[1,3]dioxolo[4,5- against Aeromonassalmonicid.

g]quinoline- 7-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C13H11NO5, 261.23 g/mol Quinolone antibiotic Uroxin

Dipole Moment (Debye) Molecular Volume Surface Area 4.23 Debye 249.89 Åᶾ 259.24 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 77.772 Ų 14698-29-4 0.017 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 1 6

References and summary a. MOA The mechanism of action was determined from a protein conformation which binds to gyrase. (Drlica, Karl. "Mechanism of fluoroquinolone action." Current opinion in microbiology 2.5 (1999): 504-508.

b. Source Oxolinic Acid is a quinolone antibiotic that aids in the treatment of ear infections. (Blondeau, Joseph M. "Fluoroquinolones: mechanism of action, classification, and development of resistance." Survey of ophthalmology 49.2 (2004): S73-S78.

c. Cell line Test (MIC) A cell line test of 0.5 μg/mL was carried out to test for inhibition against Aeromonassalmonicid. (Samuelsen, Ole Bent, et al. "Single-dose pharmacokinetic study of oxolinic acid and vetoquinol, an oxolinic acid ester, in Atlantic salmon held in seawater and in vitro antibacterial activity against Aeromonassalmonicid ." Aquaculture 187.3 (2000): 213-224. d. Human clinical trials A clinical trial was carried out to determine the efficacy of Oxolinic Acid in Scophthalmus maximus. (Poher, I. "Pharmacokinetics of a discontinuous absorption process of oxolinic acid in turbot, Scophthalmus maximus, after a single oral administration." Xenobiotica 28.11 (1998): 1061-1073.

e. Review Article Oxolinic Acid was tested against a pine wilt disease. (Kwon, Hyeok Ran, et al. "Suppression of pine wilt disease by an antibacterial agent, oxolinic acid." Pest management science 66.6 (2010): 634-639.

Oxolinic Acid was tested against bacteria in shrimp ponds. (Tendencia, Eleonor A. "Level and percentage recovery of resistance to oxytetracycline and oxolinic acid of bacteria from shrimp ponds." Aquaculture 213.1 (2002): 1-13.

Antibiotic nameOxytetracycline Diseases treatedChlamydia m log P -1.606

SMILESCN(C)[C@@H]3C(\O)=C(\C(N)=O)C IUPAC4S,4aR,5S,5aR,6S,12aS) -4- MIC values32 µg/ml, Mycoplasma bovis. (=O)[C@@]4(O)C(/O)=C2/C(=O)c1c(cccc1 (dimethylamino)- O)[C@@](C)(O)[C@H]2[C@H](O)[C@@H] 3,5,6,10,11,12a-hexahydroxy -6- 34 methyl-1,12-dioxo- 1,4,4a,5,5a,6,12,12a- octahydrotetracene -2- carboxamide

Emp. Formula, Molar mass Antibiotic groupTetracycline Trade namesAlbaoxy

C22H24N2O9, 460.434 g/mol

Dipole Moment (Debye)3.75 Debye Molecular Volume 385.483 Å3 Surface Area367.24 Å2

Surface Area (TPSA)201.842 Å2 CAS Number2058-46-0 D/V (dipoe moment/volume)0.010 Debye/ Å3

Rotatable # bonds2 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)8 atoms)11

References and summary a. MOAOxytetracycline interferes with the ability of bacteria to produce essential proteins. With these proteins absent, the bacteria cannot grow. Oxytetracycline stops the spread of infection. (Chopra, I., et al. Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance. Microbiol Mol Biol Rev. 65(2): 232–260, 2001)

b. Source Oxytetracycline come from Streptomyces rimosus. (Al-Jawadi, M., et al. Identification of Some Streptomycetes producing Oxytetracycline. Microbiology. 131 (9), p. 2241-2244, 1985)

c. Cell line TestMIC= 32 µg/ml of oxytetracycline against recent field isolates of Mycoplasma bovis. (Ayling R., et al., Comparison of in vitro activity of , , florfenicol, oxytetracycline, spectinomycin and tilmicosin against recent field isolates of Mycoplasma bovis. Vetinary Journal. 146 (16), 745-747, 2004) (MIC)

d. Human clinicalA comparison of oral azithromycin with oxytetracycline in eye ointment (once daily for five days every four weeks, total of six treatments. Children were administered 20 mg/kg once a day= single dose. (Dawson, C., et al. A Comparison of oral Azithromycin with tropical ocytetracycline/Polymyxin for the treatment of Trachoma in Children. Clinical Infectious Diseases. 24 (3); p. 363-368, 1997) trials

e. Review Article (Rose, P., et al. Fate of oxytetracycline in streams receiving aquaculture discharges: model simulations. Environ Toxicol Chem 24: p. 40–50, 2005.)

Antibiotic name Diseases treated Intestinal m log P = -6.036 Paromomycin Infections and Leishmaniasis

SMILES IUPAC MIC values

O=S(=O)(O)O.O([C@H]3[C@H](O[C@@H] (2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)- H. pylori: 0.5-4 mg/L 4,6-diamino-2-[(2S,3R,4R,5R)-4- 2O[C@H](CO)[C@@H](O[C@H]1O[C@@ [(2R,3R,4R,5R,6S)- H](CN)[C@@H](O)[C@H](O)[C@H]1N)[C 3-amino-6-(aminomethyl)-4,5-dihydroxy-oxan- 2-yl] @H]2O)[C@@H](O)[C@H](N)C[C@@H]3 oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2- N)[C@H]4O[C@@H]([C@@H](O)[C@H]( yl]oxy- 3-hydroxy-cyclohexyl]oxy-2- O)[C@H]4N)CO (hydroxymethyl)oxane-3,4-diol

Emp. Formula, Molar mass Antibiotic group Trade names

Emp. Formula: C23H47N5O18S Aminoglycoside Antibiotics Humatin, Paromycin Molar mass: 615.629 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3.75 Debye 530.695 Å3 575.30 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 347.343 Å2 1263-89-4 0.007 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 18 19

References and summary a. MOA Paromomycin inhibits protein synthesis interacting with the rRNA subunits. (Jhingran, A., Chawla, B., Saxena, S., Barrett, MP., Madhubala, R., Paromomycin: uptake and resistance in Leishmania donovani, Mol Biochem. Parasitol., 164(2), 111-117, 2009). 1

b. Source Streptomyces krestomuceticus (Meyer, JM., Ryu, Seonyoung, Pendland, SL., Kanyok, TP., Danziger, LH., In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori, J. Antimicrob. Chemother., 43(3), 403-406, 1999). 2

c. Cell line Test (MIC) H. pylori: 0.5-4 mg/L (Meyer, JM., Ryu, Seonyoung, Pendland, SL., Kanyok, TP., Danziger, LH., In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori, J. Antimicrob. Chemother., 43(3), 403-406, 1999). 2

d. Human clinical Leishmaniasis, Cutaneou: Phase 2 trials Visceral Leishmaniasis: Phase 3 Cryptosporidiosis HIV Infections: Phase 2

e. Review Article 1) Jhingran, A., Chawla, B., Saxena, S., Barrett, MP., Madhubala, R., Paromomycin: uptake and resistance in Leishmania donovani, Mol Biochem. Parasitol., 164(2), 111-117, 2009. 2) Meyer, JM., Ryu, Seonyoung, Pendland, SL., Kanyok, TP., Danziger, LH., In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori, J. Antimicrob. Chemother., 43(3), 403-406, 1999.

Antibiotic name Diseases treated m log P Pazufloxacin Legionnaire’s Disease, gonorrhea = -0.439

SMILES IUPAC MIC values C[C@H]1COC2=C3N1C=C(C(=O)C3=CC (3S)-10-(1-Aminocyclopropyl)-9- 64 µg/mL, Psuedomonas aeruginosa HU (=C2C4(CC4)N)F)C(=O)O fluoro-2,3-dihydro-3-methyl-7- 2000-E oxo-7H-pyrido[1,2,3-de]-1,4- benzoxazine-6-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H15FN2O4, 318.3 g/mol Third-generation quinolones Pasil, Pazucross

Dipole Moment (Debye) Molecular Volume Surface Area 5.81 Debyes 295.85 Å3 312.92 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 94.561 Å2 127045-41-4 0.0196 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA: Inhibits DNA gyrase activity which leads to no DNA or RNA synthesis. [Andriole, V., Qunolones: Past, present, and future, Clin. Inf. Dis., 41(supplement 2), pp. S113-S119, 2005]

b. Source: Pazufloxacin is a synthetic antibiotic created by Pazufloxacin Toyama Chemical Corporation. [Johnson, A., Pazufloxacin Toyama Chemical Co., Curr.Opin. Investig. Drugs, 1(1), pp. 52-57, 2000]

c. Cell line Test (MIC): In this study, different strains of Pseudomonas aeruginosa are exposed to pazufloxacin and other antibiotics to determine the minimal inhibitory concentration of these antibiotics. [Muramatsu, H., Horii, T., Takeshita, A., Hashimoto, H., Maekawa, Characterization of fluoroquinolone and carbapenem susceptibilities in clinical isolates of levofloxacin-resistant Pseudomonas aeruginosa, Chemother., 51(1), pp. 70-75, 2005]

d. Human clinical trials: In this clinical trial, male patients who had gonoccocal urethritis due to an infection with Neisseria gonorrhoeae were treated with pazufloxacin at Kyushu University Hospital. [Tanaka, M., Matsumoto, T., Sakumoto, M., Takahashi, K., Saika, T., Kabayashi, I., Kumazawa, J., Reduced clinical efficacy of pazufloxacin against gonorrhea due high prevalence of quinolone-resistant isolates with the GyrA mutation. The pazufloxacin STD group., Antimicrob. Agents Chemother., 42(1), pp. 579-582, 1998]

e. Review Article: In this article, the history, uses, and activity of quinolones is discussed and summarized. [Andriole, V., Qunolones: Past, present, and future, Clin. Inf. Dis., 41(supplement 2), pp. S113-S119, 2005]

Antibiotic name Diseases treated m log P Penicillin G Treats syphilis and meningitis =1.817

SMILES IUPAC MIC values

CC1([C@@H](N2[C@H](S1)[C@@ (2S,5R,6R)-3,3-dimethyl-7- 0.06 µg/mL when tested on in vitro H](C2=O)NC(=O)Cc3ccccc3)C(=O)O oxo-6-(2-phenylacetamido)-4- viruses. )C thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H18N2O4S Narrow Spectrum Pzierpen 334.396 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 5.19 Debye 321.79 Å3 74.258 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 86.706 Å2 61-33-6 0.0161 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 2 6

References and summary a. MOAThe mechanism of action is inhibiting the cell wall synthesis. ( Tipper, Donald J., and Jack L. Strominger. "Mechanism of action of penicillin’s: a proposal based on their structural similarity to acyl-D- alanyl-D-alanine."Proceedings of the National Academy of Sciences of the United States of America 54.4 (1965): 1133.)

b. SourceThe natural source of penicillin is from the fungi Penicillium. (Fleming, Alexander. "On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenza." British journal of experimental pathology 10.3 (1929): 226.)

c. Cell line Test (MIC)The MIC value was 0.06 µg/mL when tested on in vitro viruses to test the time it takes to kill the bacteria on an agar plate. (Pankuch, G. A., M. R. Jacobs, and P. C. Appelbaum. "Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, , ciprofloxacin, and vancomycin by using time-kill methodology." Antimicrobial agents and chemotherapy 38.9 (1994): 2065- 2072. d. Human clinical trialsTreatment of Group A Beta Hemolytic Streptococcal Pharyngitis in Children in Low Resource Settings. The purpose of this trial was to test the microbiological effects of two different treatments; the first was a single dose of intramuscular benzathine penicillin G (IM BPG) vs. a 10-day daily dose of amoxicillin for the treatment of GABHS pharyngitis in children in low resource setting. The trial has completed Phase4.

e. Review Article"Prophylaxis with oral penicillin in children with sickle cell anemia, Gaston, Marilyn H., et al. "Prophylaxis with oral penicillin in children with sickle cell anemia." New England Journal of Medicine 314.25 (1986): 1593-1599. The article discusses the effectiveness Penicillin G has against treating children infected with sickle cell anemia.

Antibiotic name Diseases treated Streptococcal m log P Penicillin V pharyngitis caused by S. pyogenes = 1.817

SMILES IUPAC MIC values OC(=O)[C@@H]2N3C(=O)[C@@H] 3,3-Dimethyl-7-oxo-6-(2- 0.5 µg/ml of penicillin V was shown (NC(=O)Cc1ccccc1)[C@H]3SC2(C)C phenoxyacetamido)-4-thia-1- to inhibit the growth of N. azabicyclo[3.2.0]heptane-2- mentingitidis. carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H18N2O5S Peniicillins Beepen-VK, Betapen-VK, Ledercillin 350.39 g/mol VK

Dipole Moment (Debye) Molecular Volume Surface Area 4.52 Debye 331.53 Å3 358.64 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 83.413 Å2 87-08-1 0.0136 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 2 6

References and summary a. MOA Penicillin V inhibits the growth of bacteria by inhibiting the synthesis of cellular peptidoglycan layer of the bacterial cell wall. (Izaki, K., Matsuhanshi, M., Strominger, J. L. Biosynthesis of the Peptidoglycan of Bacterial Cell Walls: XIII. PEPTIDOGLYCAN TRANSPEPTIDASE AND d-ALANINE CARBOXYPEPTIDASE: PENICILLIN-SENSITIVE ENZYMATIC REACTION IN STRAINS OF ESCHERICHIA COLI, J. Biol. Chem. 243, 3180-3192, 1968.)

b. Source Penicillin V was semi synthetically derived by modifying the natural compound produced by the Penicillium chrysogenum. (Barber, M., Waterworth, P. M., Antibacterial Activity of the Penicillins, Br. Med. J., 1(5288), 1159-1164, 1962.)

c. Cell line Test (MIC) 0.5 µg/ml of penicillin V was shown to inhibit the growth of N. mentingitidis. (Garrod, L. P., The Relative Antibacterial Activity of Four Penicillins, Br. Med. J., 2(5214), 1695-1696, 1960.)

d. Human clinical trials Out of 243 patients enrolled, 58 patients were evaluated for the efficacy of Penicillin V in treating streptococcal pharyngitis. The cure rate for Penicillin treated group was 98%. (Levenstein, J. H. Clarithromycin versus penicillin in the treatment of streptococcal pharyngitis, J. Antimicrob. Chemother., 27(suppl A), 67-74, 1991.)

e. Review Article [1]. Nathwani, D., Wood, M. J., Penicillins: A current review of their clinical pharmacology and therapeutic use, Drugs, 45(6), 866-894, 1993. [2]. Wight, A. J., The penicillins, Mayo. Clin. Proc., 74(3), 290-307, 1999.

Antibiotic name Diseases treated works against m log P Pefloxacin Gram-negative and positive bacteria = -0.095

SMILES IUPAC MIC values O=C(O) \C2=C\N(c1cc(c(F)cc1C2=O) 1-ethyl-6-fluoro-7-(4- 0.25-1 µg/ml of Pefloxacin was N3CCN(C)CC3)CC methylpiperazin-1-yl)-4-oxo- shown to work against S. hominis in quinoline-3-carboxylic acid the Mueller-Hinton broth

Emp. Formula, Molar mass Antibiotic group Trade names C17H20FN3O3 Fluoroquinolone antibacterial Peflacine 333.357 g/mol agent

Dipole Moment (Debye) Molecular Volume Surface Area 6.66 Debye 329.53 Å3 349.51 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 54.917 Å2 70458-92-3 0.020 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 1 7

References and summary a. MOA Perfloxacin has been shown to inhibit the supercoiling activity of DNA Gyrase, which inhibits the bacterial growth. (Zweerink, M. M., Edison, A., Inhibition of Micrococcus luteus DNA gyrase by norfloxacin and 10 other quinolone. carboxylic acids, Antimicrob. Agents Chemother., 29(4), 598-601, 1986.)

b. Source Perfloxacin was synthetically derived from substituting piperazine at C-7. (Foroumadi, A., Emami, S., Hassanzadeh, A., Rajaee, M., Sokhanvar, K., Moshafi, M. H., Shafiee, A., Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4- thiadiazol-2-yl) and N-(5-benzylsulfonyl- 1,3,4-thiadiazol-2- yl)piperazinyl quinolone derivatives, Bioorg. Med. Chem. Lett., 15, 4488-4492, 2005.)

c. Cell line Test (MIC) 0.25-1 µg/ml of Pefloxacin was shown to work against S. hominis in the Mueller-Hinton broth. (Fass, R.J., Helsel, V.L., In vitro antistaphylococcal activity of pefloxacin alone and in combination with other antistaphylococcal drugs, Antimicrob. Agents Chemother., 31(10), 1457-1460, 1987.)

d. Human clinical trials 400 mg of Perfloxacin given orally to forty-six patients with enteric fever showed high cure rates within five to seven days. (Unal, S., Hayran, M., Tuncer, S., Gür, D., Uzun, O., Akova, M., Akalin, H. E., Treatment of enteric fever with pefloxacin for 7 days versus 5 days: a randomized clinical trial, Antimicrob. Agents Chemother., 40(2), 2898-2900, 1996.) e. Review Article [1]. Hooper, D. C., Wolfson, J. S., The Fluoroquinolones: Pharmacology, Clinical Uses, and Toxicities in Humans, Antimicrob. Agents Chemother., 28(5), 716-721, 1985. [2]. Paton, J.H., Reeves, D.S., Fluoroquinolone Antibiotics, Drugs, 36(2), 193-228, 1988.

Antibiotic name Pivmecillinam Diseases treated lower urinary m log P 5.828 tract infections

• SMILES IUPAC 2,2- MIC values active against E. coli with CC1(C(N2C(S1)C(C2=O)N=CN3CCC dimethylpropanoyloxymethyl MIC values around 0.125 – 0.5 mg/

CCC3)C(=O)OCOC(=O)C(C)(C)C)C (2S,5R,6R)-6-[(azepan-1-

ylmethylene)amino]-3,3-

dimethyl-7-oxo-4-thia-1-

azabicyclo[3.2.0]heptane-2-

carboxylate

Emp. Formula, Molar mass C H N O S Antibiotic group Peniclillins Trade names Selexid, Penomax and 21 33 3 5 439.569 g/mol Coactabs

Dipole Moment (Debye) 4.06 Debye Molecular Volume 410.62 Å3 Surface Area 446.37 Å2

Surface Area (TPSA) 88.521 Å2 CAS Number 0032886-97-8 D/V (dipoe moment/volume) 0.00988 Debye/ Å3

Rotatable # bonds 8 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 0 atoms) 8

References and summary a. MOA This drug acts by inhibiting the synthesis of bacterial cell walls. (Fisher, J. F.; Meroueh, S. O.; Mobashery, S. 2005. "Bacterial Resistance to β-Lactam Antibiotics: Compelling Opportunism, Compelling Opportunity†". Chemical Reviews 105 : 395–424.

b. Source Pivmecillinam is the pivaloyloxymethyl ester of . (Pham P., Bartlett J.G.2008. "Amdinocillin (Mecillinam)". Point-of-Care Information Technology ABX Guide. Johns Hopkins University)

c. Cell line Test In 216 patients with a bacteriologically confirmed, acute, uncomplicated, urinary tract infection , the clinical and bacteriological efficacy of a 3-day course of pivmecillinam, 200 mg three times daily, was compared with that of a 7-day course of cephalexin, 250 mg four times daily. (Menday, A. P. 2000. Comparison of pivmecillinam and cephalexin in acute uncomplicated urinary tract infection. International journal of antimicrobial agents, 13:183-187. (MIC) d. Human clinical Oral administration of antibiotics for treatment of urinary tract infections (UTIs) can cause ecological disturbances in the normal intestinal microflora. Pivmecillinam affects the intestinal microflora, suppressing Escherichia coli, but does not have a major effect on the anaerobic microflora. (Edlund, C., & Nord, C. E. 2000. Effect on the human normal microflora of oral antibiotics for treatment of urinary tract infections. Journal of Antimicrobial Chemotherapy, 46:41-48.) trials e. Review Article Pivmecillinam is the pro-drug of mecillinam, a β-lactam antibiotic with a novel site of action and with specific and high activity against Gram-negative organisms such as Escherichia coli and other Enterobacteriaceae. (Graninger, W. 2003. Pivmecillinam—therapy of choice for lower urinary tract infection. International journal of antimicrobial agents, 22:73-78.)

Antibiotic name Diseases treated m log P Pipemidic acid Urinary tract infections =0.307

SMILES IUPAC MIC values CCN1C=C(C(=O)C2=CN=C(N=C21)N3CCNC 8-Ethyl-5-oxo-2-piperazin-1-yl- 50-100 µg/mL, Chylamdia trachomatis C3)C(=O)O 5,8-dihydropyrido[2,3- d]pyrimidine-6-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C14H17N5O3, 303.32 g/mol First-generation quinolones Dolcol

Dipole Moment (Debye) Molecular Volume Surface Area 5.77 Debyes 294.16 Å3 318.59 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 100.353 Å2 51940-44-4 0.0196 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 2 8

References and summary a. MOA: Pipemidic acid inhibits DNA synthesis. [Heesen, F., Muytjens, H. In vitro activities of ciprofloxacin, Norfloxacin, pipemidic acid, cinoxacin, and nalixidic acid against Chylamdia trachomatis, Antimicrob. Ag. Chemother., 25(1), pp. 123-124, 1984]

b. Source: Pipemidic acid is derived from piromidic acid. [Crumplin, G., Aspects of chemistry in the development of the 4-quinolone antibacterial agents, Rev. Inf. Dis., 10(supplement 1), pp. S2-S8, 1988]

c. Cell line Test (MIC): Pipemidic acid inhibits the growth of Chylamdia trachomatis at minimum concentrations between 50 and 100 µg/mL. [Heesen, F., Muytjens, H., In vitro activities of ciprofloxacin, Norfloxacin, pipemidic acid, cinoxacin, and nalixidic acid against Chylamdia trachomatis, Antimicrob. Ag. Chemother., 25(1), pp. 123-124, 1984]

d. Human clinical trials: Urinary tract infections were treated using norfloxacin and pipemidic acid in Spain. This study was conducted in Hospital La Fe. In Valencia, Spain. [The Spanish Multicenter Study Group, Clinical experience with norfloxacin for urinary tract infections in Spain, Rev. Inf. Dis., 10(1), pp. S172-S173, 1988]

e. Review Article: In this study, pipemidic acid’s activity and therapeutic aspects are summarized. [Sharma, P., Jain, A., Jain, S., Fluoroquinolone antibacterials: a review on chemistry, microbiology and therapeutic prospects, Acta Potoniae Pharmaceutic Drug Research, 66(6), pp. 587-604, 2009]

Antibiotic name Diseases treated m log P Piperacillin Pneumonia and Appendicitis = 0.737

SMILES IUPAC MIC values O=C(O)[C@@H]3N4C(=O)[C@@H] (2S,5R,6R)-6-{[(2R)-2-[(4-ethyl- ≤ 8 μg/ml when used against (NC(=O)[C@@H](c1ccccc1)NC(=O) 2,3-dioxo-piperazine-1- Klebsiella pneumonia N2C(=O)C(=O)N(CC)CC2)[C@H]4S carbonyl)amino]-2-phenyl- C3(C)C acetyl]amino}-3,3-dimethyl-7- oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid Emp. Formula, Molar mass Antibiotic group Trade names C23H27N5O7S, 517.563 g/mole Penicillin Pipracil

Dipole Moment (Debye) Molecular Volume Surface Area 4.55 Debye 485.93 Å3 513.11 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 128.757 Å2 61477-96-1 0.00936 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 12

References and summary a. MOA Penicillin’s mechanism of action is the inhibition of the peptidoglycan synthesis that is present in bacterial cell walls. (Kohanski, M., Dwyer, D., and Collins, J., How Antibiotics Kill Bacteria: From Targets to Networks, Nature Reviews Microbiology, Vol. 8, p. 423-435, 2010)

b. Source Penicillin is derived from Penicillium chrysogenum. (Pirt, S., and Righelato, R., Effect of Growth Rate on the Synthesis of Penicillin by Penicillium chrysogenum in Batch and Chemostat Cultures, Applied Microbiology, Vol. 15, No. 6, p. 1284-1290, 1967)

c. Cell line Test (MIC) Piperacillin was tested on Klebsiella pneumoniae. (Babini, G., and Livermore, D., Are SHV β- Lactamases Universal in Klebsiella pneumonia, Antimicrobial Agents and Chemotherapy, Vol. 58, Issue 4, p. 2230, 2000)

d. Human clinical trials Piperacillin was used on diabetic foot infections that were present on 576 patients. (Lipsky, B., et al., Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial, The Lancet, Vol. 366, p. 1695-1703, 2005)

e. Review Article A review article on the use of piperacillin in the treatment of colonic diverticular disease. (Tursi, A., and Papagrigoriadis, S., Review article: the current and evolving treatment of colonic diverticular disease, Alimentary Pharmacology and Therapeutics, Vol. 30, Issue 6, p. 532-546, 2009)

Antibiotic name Diseases treated urinary tract m log P Piromidic Acid and intestinal infections 1.414

SMILES IUPAC MIC values CCN1C=C(C(=O)C2=CN=C(N=C21)N3CCCC 8-Ethyl-5-oxo-2-pyrrolidin-1-yl- Pseudomonas aeruginosa; 12.5 µg/mL 3)C(=O)O 5,8-dihydropyrido[2,3- d]pyrimidine-6-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C14H16N4O3, 288.3018 Quinolones Bactramyl, Panacid

Dipole Moment (Debye) Molecular Volume Surface Area 5.23 243.96 Å3 264.94 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 88.326 Å2 19562-30-2 0.021 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 1 7

References and summary a. MOA Piromidic Acid is a first generation Quinolone. First and second generation quinolones selectively inhibit the topoisomerase II ligase domain in the bacterial cell leading to DNA fragmentation . (Oliphant, Catherine M., Gary M. Green. “Quinolones: A Comprehensive Review”. American Family Physician, Volume 65, Number 3. 2002)

b. Source Piromidic acid is a synthetic antibiotic derived from Nalidixic acid, a compound isolated from the synthesis process of quinine. (Andersson, Monique I., Alasdair P. MacGowan. “Development of the quinolones”. Journal of Antimicrobial Chemotherapy 51, Suppl. S1, 1–11. 2003)

c. Cell line Test (MIC) Cell line test to access resistance patterns were performed on Pseudomonas aeruginosa reporting MIC value of 12.5 µg/mL for parent strain. MIC spectrum reported for mutant strains ranged from 12.5 to >100 µg/mL. (Satoru Inoue, Tomio Ohue, Junichi Yamagishi, Shinichi Nakamura and Masanao Shimizu. Mode of Incomplete Cross-Resistance Among Pipemidic, Piromidic, and Nalidixic Acids. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug, 240-245, 1978.) d. Human clinical trials In a relatively recent trial of quinolones, Piromidic acid was one of the few with an inhibitory effect on hepatic stages of P. falciparum and P. yoelii yoelii. (Mahmoudi, N. et al. In Vitro Activities of 25 Quinolones and Fluoroquinolones against Liver and Blood Stage Plasmodium spp. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Aug., 2636–2639, 2003).

e. Review Article Aura R, Á G, G. H. New Perspectives: Quinolones as Complexation Agents. Acta Medica Marisiensis. 57(2), 149-154, 2011. Schmid D, Campi P, Pichler W. Hypersensitivity reactions to quinolones. Current Pharmaceutical Design. 12(26), 3313-3326, 2006.

Antibiotic name Diseases treated m log p = 2.752 Pivampicillin Sexually transmitted diseases

SMILES IUPAC MIC values O=C(OCOC(=O)C(C)(C)C)[C@@H]2N3C(=O 2,2- C. trachomatis: (0.25 mg/L) )[C@@H](NC(=O)[C@@H](c1ccccc1)N)[C Dimethylpropanoyloxymethyl (2S,5 C. trachomatis: (64-256 mg/L) @H]3SC2(C)C R,6R)-6-{[(2R)-2-amino-2-phenyl- acetyl]amino}-3,3-dimethyl-7-oxo-4- thia-1-azabicyclo[3.2.0]heptane-2- carboxylate

Emp. Formula, Molar mass Antibiotic group Trade names

Emp. Formula: C22H29N3O6S Penicillins (beta-lactam) Pondocillin Molar mass: 463.555 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 1.32 Debye 454.54 Å3 105.692 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 128.04 Å2 33817-20-8 0.003 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 3 9

References and summary a. MOA Pivampicillin inhibits the cell wall synthesis of bacteria (Kaldalu, N., Mei, R., Lewis, K., Killing by Ampicillin and Ofloxacin Induces Overlapping Changes in Escherichia coli Transcription Profile, Antimicrob Agents Chemother., 48(3), 890-896, 2004). 3

b. Source Escherichia coli (Thonus, IP., Fontijne, P., Michel, MF., Ampicillin Susceptibility and Ampicillin-Induced Killing Rate of Escherichia coli, Antimicrob Agents CH, 22(3), 386-390, 1982). 4

c. Cell line Test (MIC) C. trachomatis: (0-25 mg/L) (Møller, BR., Cramers, M., From, E., Pivampicillin in treating genital infection with Chlamydia trachomatis, Genitourin Med., 61, 264-265, 1985). 1 C. trachomatis: (64-256 gm/L) (Lassus, AB., Virrankoski, T., Reitamo, SJ., Kartamaa, M., Happonen, HP., Saikku, PA., Karvonen, PK., Lassus, JE., Pivampicillin Versus Doxycycline in the Treatment of Chlamydial Urethritis in Men, J Am Sexual Transmitted Diseases Association., 17(1), 20-22, 1990). 2 d. Human clinical trials Drug: Ampicillin. Phase 4 trial of Intra-abdominal infection Drug: Ampicillin. Phase 3 trial of HIV infections.

e. Review Article 1) Møller, BR., Cramers, M., From, E., Pivampicillin in treating genital infection with Chlamydia trachomatis, Genitourin Med., 61, 264-265, 1985. 2) Lassus, AB., Virrankoski, T., Reitamo, SJ., Kartamaa, M., Happonen, HP., Saikku, PA., Karvonen, PK., Lassus, JE., Pivampicillin Versus Doxycycline in the Treatment of Chlamydial Urethritis in Men, J Am Sexual Transmitted Diseases Association., 17(1), 20-22, 1990. 3) Kaldalu, N., Mei, R., Lewis, K., Killing by Ampicillin and Ofloxacin Induces Overlapping Changes in Escherichia coli Transcription Profile, Antimicrob Agents Chemother., 48(3), 890-896, 2004. 4) Thonus, IP., Fontijne, P., Michel, MF., Ampicillin Susceptibility and Ampicillin-Induced Killing Rate of Escherichia coli, Antimicrob Agents CH, 22(3), 386-390, 1982.

Antibiotic name Diseases treated m log P Platensimycin Tuberculosis =2.844

SMILES IUPAC MIC values O=C(O)c1c(O)c(c(O)cc1)NC(=O)CC[C@@] 3-[[3-[(1R,3R,4R,5aR,9R,9aS)- 12 µg/mL, Mycobacterium tuberculosis 5(C(=O)\C=C/[C@@]34C[C@@]2(O[C@@ 1,4,5,8,9,9a-hexahydro-3,9- H](C[C@@H]2C3)[C@H]45)C)C dimethyl-8-oxo-3H-1,4:3,5a- dimethano-2-benzoxepin-9-yl]- 1-oxopropyl]amino]-2,4- dihydroxy-benzoic acid

Emp. Formula, Molar mass Antibiotic group Trade names C24H27NO7, 441.48 g/mol Not classified N/A

Dipole Moment (Debye) Molecular Volume Surface Area 7.74 Debyes 420.89 Å3 415.72 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 133.158 Å2 835876-32-9 0.0184 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 4 8

References and summary a. MOA: Platensimycin inhibits the function of FabF (enzyme) which causes the inhibition of fatty acid synthesis. [Lu, X., You, Q., Recent advances on platensimycin: a potential antimicrobial agent, Curr. Med. Chem., 17, pp. 1139- 1155, 2010].

b. Source: Platensimycin is naturally produced by Streptomyces platensis as a metabolite. [Lu, X., You, Q., Recent advances on platensimycin: a potential antimicrobial agent, Curr. Med. Chem., 17, pp. 1139-1155, 2010].

c. Cell line Test (MIC): Mycobacterium species were exposed to platensimycin to determine this antibiotic’s MIC for each microbe. [Brown, A., Taylor, R., Bhatt, A., Fütterer, K., Besra, G., Platensimycin activity against mycobacterial β-ketoacyl- synthases, PLoS ONE, 4(7), pp.1-10, 2009].

d. Human clinical trials: Platensimycin is not ready for clinical use. However, platensimycin was tested in a mouse model, but more trials are necessary to obtain consistent results. [Allahverdiyev, A., Bagirova, M., Abamor, E., Ates, S., Koc, R., Miraloglu, M., Elcicek, S., Yaman, S., Unal, G., The use of platensimycin and platencin to fight antibiotic resistance, Inf. Drug Resist., 3(6), pp. 99-114, 2013].

e. Review Article: In this study, the history, uses, properties of the antibiotic, and detailed, updated studies on platensimycin, is reviewed. [Lu, X., You, Q., Recent advances on platensimycin: a potential antimicrobial agent, Curr. Med. Chem., 17, pp. 1139-1155, 2010].

Antibiotic name Diseases treated infections m log P Polymyxin B caused by bacteria. = -5.619

SMILES IUPAC MIC values CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O N-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18- Polymyxin B showed excellent potency tris(2-aminoethyl)-15-benzyl-3-(1- )C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(NC(= hydroxyethyl)-12-(2-methylpropyl)- against Pseudomonas aeruginosa 2 O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C) 2,5,8,11,14,17,20-heptaoxo- 1mg/ml. NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CCN)N 1,4,7,10,13,16,19-heptazacyclotricos-21- yl]amino]butan-2-yl]amino]-3-hydroxy-1- C1=O)C(C)O oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6- methyloctanamide

Emp. Formula, Molar mass Antibiotic group Trade names C56H98N16O13,1203.499 g/mol Polymyxin Not found

Dipole Moment (Debye) Molecular Volume Surface Area 38.79 Debye 1232.16 Å3 1305.76 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 400.843 Å2 1405-20-5 0.0314 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 29 available, attached to O, S, N) atoms) 23 29

References and summary a. MOA Polymyxin B (PMB) is a cationic antibiotic that interacts with the envelopes of gram-negative bacterial cells.(Krupovic M.,Daugelaviciius R.,bamford D.H. physiological effects polymyxin B induceslysis of marine pseudoalteromonads, Antimicrob. Agents Chemother.,Vol. 51(11),pg.3908-3914,August 2007.

b. Source biosynthesis of polymyxin from Bacillus Polymyxa (Paulus H.,Edith G.,The biosynthesis of polymyxin B by growin culturs of Bacillus polymyxa ,J. Biol. Chem.,Vol. 239(8),pg. 865-871, 1964

c. Cell line Test (MIC) Polymyxin B showed excellent potency and spectrum against Pseudomonas aeruginosa 1mg/ml.(Gales A.C.,Jones R.N.,Sader H.S., Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme, Clin. Microbiol. Inf.,Vol .12(4),pg. 315-321,April 2006. d. Human clinical trials 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h standard therapy. PMX was well tolerated and showed no significant side effects.( Vincent, J.L., Laterre, P.F., Cohen, J., Burchardi, H., Bruining, H.L., Francisco A., Wittebole X., De Backer D., Brett S., Marzo D., Nakamura H., John S.,Clin. Asp.,Vol. 23(5),pg. 400-405,May 2005.

e. Review Article 1. Gonzalo J. M., Norio K.,Kuo J.F., Polymyxin B is a more selective inhibitor for phospholipid-sensitive Ca2+- dependent protein kinase than for calmodulin-sensitive Ca2+-dependent protein kinase, Biochem. Biophys. Resear. Comm.,Vol. 109(4),pg. 1129-1133,December 1982. 2. Krupovic M.,Daugelaviciius R.,bamford D.H. physiological effects polymyxin B induceslysis of marine pseudoalteromonads, Antimicrob. Agents Chemother.,Vol. 51(11),pg.3908-3914,August 2007.

Antibiotic name Diseases treated m log P Pesizolid Tuberculosis = 0.648

SMILES IUPAC MIC values C1CN(CC=C1C2=C(C=C(C=C2F)N3 5R)-3-[4-[1-[(2S)-2,3- At a concentration of 1 mg/L, C[C@@H](OC3=O)COC4=NOC=C4 Dihydroxypropanoyl]-3,6- pesizolid inhibits 90% growth of )F)C(=O)[C@H](CO)O dihydro-2H-pyridin-4-yl]-3,5- Staphylococcus aureus. difluorophenyl]-5-(1,2- oxazol-3-yloxymethyl)-1,3-

oxazolidin-2-one

Emp. Formula, Molar mass Antibiotic group Trade names C21H21F2N3O7 Oxazolidinone AZD2563 465.40 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3.53 Debye 422.59 Å3 450.26 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 105.567 Å2 252260-02-9 0.0084 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 9 available, attached to O, S, N) atoms) 2 10

References and summary a. MOA Similar to other oxazolidinones, posizolid, inhibits the protein synthesis by interfering with 50S ribosomal subunit of the bacteria. (Fines, M. and Leclercq, R., Activity of linezolid against gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors J. Antimicrob. Chemother., 45, 797–802, 2000.)

b. Source Posizolid is a synthetically derived antibiotic. (Phillips, O. A, et al., Synthesis and antibacterial activity of new N-linked 5-triazolylmethyl oxazolidinones., Bioorgan. Med. Chem. 13(2), 4113-4123, 2005.)

c. Cell line Test (MIC) At a concentration of 1 mg/L, pesizolid inhibits 90% growth of Staphylococcus aureus. (Wookey, A., et al., AZD2563, a novel oxazolidinone: definition of antibacterial spectrum, assessment of bactericidal potential and the impact of miscellaneous factors on activity in vitro., Clin. Microbiol. Infect., 10(3), 247-254, 2004.) d. Human clinical trials AZN2563 is discontinued from the market. (Sood et al., Antimycobacterial Activities of Oxazolidinones: A Review., Inf. Dis.,6, 343-354, 2006.)

e. Review Article [1]. Sood R., Bhadauriya, T., Rao, M., Gautum, R., Malhotra, S., Barman, T. K., Upadhyay, D. J., Rattan, A., Antimycobacterial Activities of Oxazolidinones: A Review., Inf. Dis.,6, 343-354, 2006. [2]. Hutchinson, D. K., Oxazolidinone antibacterial agents: a critical review., Curr. Top Med. Chem., 3(9), 1021-1042, 2003.

Antibiotic name Diseases treated m log P Pristinamycin Eczematous Skin Disease =0.709

SMILES IUPAC MIC values O=C([C@H](CC2=CC=C(N(C)C)C=C2)N(C)[C 8,9,14,15,24,25-hexahydro-14- 32 µg/ml was obtained when tested for @]([C@H]6N(CCC6)C5=O)=O)N1[C@H]([C hydroxy-4,12-dimethyl-3-(1- Staphylococcus aureus. @](N[C@H](C(O[C@H](C)[C@@H](C(N[C methylethyl)(3R,4R,5E,10E,12E,1 @@H]5CC)=O)NC(C4=NC=CC=C4O)=O)=O 4S)-3H-21,18-nitrolo-1H,22H- )[C@]3=CC=CC=C3)=O)CC(CC1)=O pyrrolo\[2,1-c\]\[1,8,4,19\]- dioxadiazacyclotetracosine- 1,7,16,22(4H,17H)-tetrone Emp. Formula, Molar mass Antibiotic group Trade names C28H35N3O7, 525.59 g/mol Pyostacine

Dipole Moment (Debye) Molecular Volume Surface Area 9.30 Debye 806.65 Å3 205.06 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 227.955 Å2 21411-53-0 0.012 D/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 4 18

References and summary a. MOA Pristinamycin inhibits protein synthesis at the bacterial 70S ribosome. (Vannuffel, P., et al. Mechanism of action of streptogramins and macrolides. Drugs, (51)1, p. 20-30, 1996).

b. Source Pristinamycin is a naturtally occurring antibiotic obtained from Streptomyces pristinaespiralis. (Barriere, J. C., et al. Antimicrobial activity against Staphylococcus aureus of semisynthetic injectable streptogramins: RP 59500 and related compounds. Journal of Antimicrobial Chemotherapy. p. 1-8, 1992).

c. Cell line Test (MIC) MIC values of 32 µg/ml was obtained when tested for Staphylococcus aureus. (Fernández, P., et al. Enhancement of the susceptibility of Staphylococcus aureus to phagocytosis after treatment with fosfomycin compared with other antimicrobial agents. Chemotherapy. (41)1, p. 45-49, 1995).

d. Human clinical trials This study was carried out to compare the of Pristinamycin and penicillin in treatment of erysipelas in adults. (Bernard, P., et al. Oral pristinamycin versus standard penicillin regimen to treat erysipelas in adults: randomised, non-inferiority, open trial. p. 864, 2002).

e. Review Article A review on articles that discussed the efficacy of Pristinamycin in treating osteoarticular infections was carried out. (Ng, J., et al. Successful oral pristinamycin therapy for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus spp. Journal of Antimicrobial Chemotherapy (55)6, p. 1008-1012, 2005).

Antibiotic name Diseases treated m log P Prulifloxacin Diarrhea, Urinary tract infection = 0.16

SMILES IUPAC MIC values CC1N2C3=CC(=C(C=C3C(=O)C(=C2S1)C(=O (RS)-6-Fluoro-1-methyl-7-[4-(5- 8µg/ml was determined when testing )O)F)N4CCN(CC4)CC5=C(OC(=O)O5)C methyl-2-oxo-1,3-dioxolen-4- for respiration and otorhinological yl)methyl-1-piperazinyl]-4-oxo- infections 4H-[1,3]thiazeto[3,2-a]quinoline- 3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C21H20FN3O6S, 461.463403 g/mol Quinolone Quisnon

Dipole Moment (Debye) Molecular Volume Surface Area 6.64 Debye 417.56 Å3 84.53 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 109.13 Å2 123447-62-1 0.016 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 4 available, attached to O, S, N) atoms) 1 9

References and summary a. MOA The mechanism of action of prulifloxacin involves the contacts with both DNA gyrase, and topoisomerase IV. (Hooper, C., Mode of action of fluoroquinolones. (58)2, p. 6-10, 1999).

b. Source Prulifloxacin is a synthetic antibiotic produced by several artificial processes. (Ziemska, J., et al. New perspectives on antibacterial drug research. Central European Journal of Biology (8)10, p. 943-957, 2013).

c. Cell line Test (MIC) 8µg/ml was determined when testing for respiration and otorhinological infections. (Hasegawa, M., et al. Antibacterial activity of against major organisms detected from patients with respiratory or otorhinological infections: comparison with the results obtained from organisms isolated about 10 years ago. Journal of infection and chemotherapy (12)3, p.152-156, 2006). d. Human clinical trials A clinical test was carried out on patients for four weeks to test the efficacy of prulifloxacin versus levofloxacin in treating Chronic Bacterial Prostatitis. (Giannarini, G., et al. Prulifloxacin versus levofloxacin in the treatment of chronic bacterial prostatitis: a prospective, randomized, double-blind trial. Journal of Chemotherapy (19)3, p. 304-308, 2007).

e. Review Article Nine articles on prulifloxacin were reviewed focusing on its use beyond respiratory and urinary tract infections. (Rafailidis, P., et al. Prulifloxacin: a review focusing on its use beyond respiratory and urinary tract infections. International journal of antimicrobial agents (37)4, p.283-290, 2011).

Antibiotic name Diseases treated m log P Pyrazinamide Treats Tuberculosis =-0.711

SMILES IUPAC MIC values O=C(N)c1nccnc1 pyrazine-2-carboxamide )The MIC value is between the values of 6.25-50 µg/ mL when tested on M tuberculosis

Emp. Formula, Molar mass Antibiotic group Trade names C5H5N3O Carboxamide group Rifater 123.11 g/moll

Dipole Moment (Debye) Molecular Volume Surface Area 3.62 Debye 118.70 Å3 53.046 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 68.878 Å2 98-96-4 0.0305 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 1 available, attached to O, S, N) atoms) 2 4

References and summary a. MOAThe mechanism of action is inhibiting the membrane transport function in Mycobacterium tuberculosis.( Zhang, Ying, et al. "Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid." Journal of Antimicrobial Chemotherapy 52.5 (2003): 790-795.)

b. SourceThe source of Pyrazinamide is being a prodrug that is synthetically converted into an active drug.( Zhang, Ying, et al. "Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid." Journal of Antimicrobial Chemotherapy 52.5 (2003): 790-795.)

c. Cell line Test (MIC)The MIC value is between the values of 6.25-50 µg/ mL when tested on M tuberculosis at a pH level of 5.5.( ZHANG, YING, SALLIE PERMAR, and ZHONGHE SUN. "Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide." Journal of medical microbiology 51.1 (2002): 42-49.)

d. Human clinical trialsProphylaxis Against Tuberculosis (TB) in Patients With Human Immunodeficiency Virus (HIV) Infection and Confirmed Latent Tuberculosis Infection. The trail was to test what drug between pyrazinamide and isoniazid was more effective in treating HIV infected patients with tuberculosis. The study has completed Phase 4.

e. Review ArticleThe curious characteristics of pyrazinamide: a review(Zhang, Y., and D. Mitchison. "The curious characteristics of pyrazinamide: a review." The International Journal of Tuberculosis and Lung Disease 7.1 (2003): 6-21.) The article is about the history of the synthetic drug, and tests the drug has ran through.

Antibiotic name: Diseases treated: Skin infections m log P= Quinupristin due to Streptococcus Pyogenes Bacteria 1.985

SMILES: IUPAC : MIC values: N-{(6R,9S,10R,13S,15aS,18R,22S,24aS)-18- CC[C@@H]1C(=O)N2CCC[C@H]2C(=O)N([ MIC90 value is 1.0 mg/L active against in {[(3S)-1-azabicyclo[2.2.2]oct-3-ylthio]methyl- C@H](C(=O)N3C[C@H](C(=O)C[C@H]3C(= 22-[4-(dimethylamino)benzyl]- 6-ethyl-10,23- vitro VREF O)N[C@H](C(=O)O[C@@H]([C@@H](C(= dimethyl-5,8,12,15,17,21,24-heptaoxo-13- O)N1)NC(=O)C4=C(C=CC=N4)O)C)C5=CC= phenyldocosahydro-12H- pyrido[2,1- f]pyrrolo-[2,1-l][1,4,7,10,13,16] CC=C5)CS[C@@H]6CN7CCC6CC7)CC8=CC oxapentaazacyclononadecin-9-yl}-3- =C(C=C8)N(C)C)C hydroxypyridine-2-carboxamide

Emp. Formula, Molar mass: Antibiotic group: Trade names: C53H67N9O10S, 1022.239 g/mol Streptogramins Synercid

Dipole Moment (Debye)= Molecular Volume= Surface Area= 14.33 Debye 926.126 Å3 997.17 Å2

Surface Area (TPSA)= CAS Number: D/V (dipoe moment/volume)= 231.193 Å2 120138-50-3 0.0155 Debye/ Å3

Rotatable # bonds: Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N): atoms): 4 19

References and summary a. MOA: The mechanism of action of quinupristin is that protein synthesis is inhibited by conformational modification of the region of the bacterial ribosome where peptidyltrans ferase acts which in turn may decrease the hydrodytic activity of peptidyl-tRNA hydrolase leading to a tRNA auxotrophy and bacterial cell death. (Boswell, F. J., et al. "Time-kill kinetics of quinupristin/dalfopristin on Staphylococcus aureus with and without a raised MBC evaluated by two methods." Journal of Antimicrobial Chemotherapy 39.suppl 1 (1997): 29-32.)

b. Source: Quinupristin is derived from Pristinamycin IA and IIA respectively. (Boswell, F. J., et al. "Time-kill kinetics of quinupristin/dalfopristin on Staphylococcus aureus with and without a raised MBC evaluated by two methods." Journal of Antimicrobial Chemotherapy 39.suppl 1 (1997): 29-32.)

c. Cell line Test (MIC): Quinupristin is the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. (Moellering, R. C., et al. "The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium." Journal of Antimicrobial Chemotherapy 44.2 (1999): 251-261.)

d. Human clinical trials: Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included patients with infection caused by other Gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy.( Moellering, R. C., et al. "The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium." Journal of Antimicrobial Chemotherapy 44.2 (1999): 251-261.) e. Review Article Boswell, F. J., et al. "Time-kill kinetics of quinupristin/dalfopristin on Staphylococcus aureus with and without a raised MBC evaluated by two methods." Journal of Antimicrobial Chemotherapy 39.suppl 1 (1997): 29-32. Moellering, R. C., et al. "The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium." Journal of Antimicrobial Chemotherapy 44.2 (1999): 251-261. f.

Antibiotic name Diseases treated m log P Radezolid Skin infections and Pneumonia = 1.816

SMILES IUPAC MIC values CC(=O)NC[C@H]1CN(C(=O)O1)C1 N-{[(5S)-3-(2-fluoro-4′- 1 μg/ml when used against MRSA =CC=C(C(F)=C1)C1=CC=C(CNCC2 {[(1H-1,2,3-triazol-5- 11540 =CN=NN2)C=C1 ylmethyl)amino]methyl}biphe nyl-4-yl)-2-oxo-1,3- oxazolidin-5- yl]methyl}acetamide

Emp. Formula, Molar mass Antibiotic group Trade names C22H23FN6O3, 438.463 g/mol Oxazolidinone RX-1741

Dipole Moment (Debye) Molecular Volume Surface Area 3.35 Debye 428.20 Å3 461.72 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 100.174 Å2 869884-78-6 0.0078 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 3 9

References and summary a. MOA Oxazolidinones inhibit the translation of bacterial proteins. (Shinabarger, D., et al., Mechanism of action of oxazolidinones: effects of linezolid and eperezolid on translation reactions, Antimicrobial Agents and Chemotherapy, Vol. 41, No. 10, p. 2132-2136, 1997)

b. Source Oxazolidinones are synthetic antibiotics and are synthesized in multiple waty to increase effectiveness. (Comb, J., Sonication-Assisted Library Synthesis of Oxazolidinone-Carbohydrate Conjugates, Journal of Combinatorial Chemistry, Vol. 9, No. 1, p. 17-19, 2007)

c. Cell line Test (MIC) Radezolid was tested against Methicillin resistance Staphylococcus aureus. (Locke, J., et al., Structure- Activity Relationships of Diverse Oxazolidinones for Linezolid-Resistant Staphylococcus aureus Strains Possessing the cfr Methyltransferase Gene or Ribosomal Mutations, Antimicrobial Agents and Chemotherapy, Vol. 54, No. 12, p. 5337-5343, 2010) d. Human clinical trials Radezolid was used in a clinical trial treating incomplicated skin and skin structure infections. (File, T., et al., A Phase 2 Study comparing two doses of radezolid to linezolid in adults with uncomplicated skin and skin structure infections (uSSSI), 48th ICAAC, Poster L-1515c, 2008)

e. Review Article A review of pharmacokinetic drug interactions. (Bolhuis, M., et al., Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams, Pharmaceutics, Vol. 3, p. 865-913, 2011)

Antibiotic name Diseases treated m log P Rifabutin Tuberculosis, Leprosy = 3.97

SMILES IUPAC( MIC values 2 µg/mL, Mycobacterium CC(C)CN1CCC2(CC1)/N=C\3/c4c6C(=O)[C 9S,12E,14S,15R,16S,17R,18R,19R,20S, avium complex 21S,22E,24Z)-6,16,18,20-tetrahydroxy-1'- @@]5(C)O/C=C/[C@H](OC)[C@@H](C)[C isobutyl-14-methoxy-7,9,15,17,19,21,25- @@H](OC(C)=O)[C@H](C)[C@H](O)[C@H hepta-methyl-spiro[9,4-(epoxypentadeca ](C)[C@@H](O)[C@@H](C)\C=C\C=C(\C)C [1,11,13]trienimino)-2H-furo-[2',3':7,8]- naphth (=O)N \C(=C/3/N2)C(=O)c4c(O)c(C)c6O5 [1,2-d]imidazol-2,4'-piperidin]-5,10,26- (3H,9H)- trione-16-acetate

Emp. Formula, Molar mass Antibiotic group Trade names C46H62N4O11, 847.005 g/mol Rifamycins Mycobutin

Dipole Moment (Debye) Molecular Volume Surface Area 3.68 Debyes 859.66 Å3 863.89 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 205.56 Å2 72559-06-9 0.00428 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 5 15

References and summary a. MOA: Rifabutin inhibits protein synthesis. [Kunin, C., Antimicrobial activity of rifabuitn, CID, 22(supplement 1), pp.S3-S14, 1996].

b. Source: Rifabutin is a semi-synthetic antibiotic derived from Rifamycin S. [Kunin, C., Antimicrobial activity of rifabuitn, CID, 22(supplement 1), pp.S3-S14, 1996].

c. Cell line Test (MIC): In this study, Rifabutin is shown to inhibit Mycobacterium avium complex, Mycobacterium tuberculosis, and Mycobacterium leprae at various minimal concentrations. [Kunin, C., Antimicrobial activity of rifabuitn, CID, 22(supplement 1), pp.S3-S14, 1996]

d. Human clinical trials: In this study, rifabutin is being used to treat patients with crohn’s disease at the University of Central Florida. [Shafran, I., Kugler, L., El-Zaatari, F., Naser, S., Sandoval, J., Open clinical trial of rifabutin and clarithromycin therapy in crohn’s disease, Dig. Liver Dis., 34(1), pp. 22-28, 2002].

e. Review Article: In this article, Rifabutin’s effects on refractory Helicobacter pylori have been documented based on various studies. [Gisbert, J., Calvet, J., Review article: rifabutin in the treatment of refractory Helicobacter pylori infection, Aliment Pharmacol. Ther., 35(2), pp. 209-221, 2012].

Antibiotic name Diseases treated m log P Rifampin Tuberculosis, inactive meningitis 2.615

SMILES IUPAC MIC values C[C@H]1/C=C/C=C( \C(=O)NC2=C(C(=C3C( (7S,9E,11S,12R,13S,14R,15R,16R, Enterococcus faecium; 0.016 µg/mL =C2O)C(=C(C4=C3C(=O)[C@](O4)(O/C=C/[ 17S,18S,19E,21Z)-2,15,17,27,29- (parent strain) C@@H]([C@H]([C@H]([C@@H]([C@@H] pentahydroxy-11-methoxy- ([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC 3,7,12,14,16,18,22-heptamethyl- )C)C)O)O)/C=N/N5CCN(CC5)C)/C 26-{(E)-[(4-methylpiperazin-1- yl)imino]methyl}-6,23-dioxo- 8,30-dioxa-24- Emp. Formula, Molar mass Antibiotic group Trade names C43H58N4O12, 822.94 g/mol Rifamycin Rifadin, Rimactane

Dipole Moment (Debye) Molecular Volume Surface Area 4.06 820.15 Å3 805.90 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 220.156 Å2 13292-46-1 .005 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 16 6

References and summary a. MOA Rifampin forms a complex with RNA polymerase and inhibits the initiation of transcription and sterically hinders translocation. (Reisbig, Richard R., A. Young M. Woody, and Robert W. Woody Rifampicin as a spectroscopic probe of the mechanism of RNA polymerase from E. coli Biochemistry 21 (1), 196-200, 1982

b. Source Rifampin is a semisynthetic derivative of rifamycin antibiotics which are produced by the fermentation of a strain of Streptomyces mediterranei. (Barry C. Lessons from seven decades of antituberculosis drug discovery. Current Topics In Medicinal Chemistry, 11(10), 1216-1225, 2011.)

c. Cell line Test (MIC) Cell line tests on Enterococcus faecium showed MIC values ranging from 0.016 µg/mL, in parent strains of the bacteria, to upwards of 256 µg/mL in mutated generations which indicates a development of resisiteance. (V. I. Enne, A. A. Delsol, J. M. Roe, and P. M. Bennett Rifampicin resistance and its fitness cost in Enterococcus faecium . Journal of Antimicrobial Chemotherapy. 53 (2), 203-207, 2004)

d. Human clinical trials In a comparative study of clinical trials, it was found that rifampin in conjunction with penicillin V. was more effective than mono-therapy at treating streptococcal infections, specifically pharyngitis caused by β-hemolytic streptococci. (Bliziotis I, Ntziora F, Lawrence K, Falagas M. Rifampin as adjuvant treatment of Gram-positive bacterial infections: a systematic review of comparative clinical trials. European Journal Of Clinical Microbiology & Infectious Diseases. 26(12), 849-856, 2007.)

e. Review Article Pachón-Ibáñez M, Docobo-Pérez F, Pachón J, et al. Efficacy of rifampin, in monotherapy and in combinations, in an experimental murine pneumonia model caused by panresistant Acinetobacter baumannii strains. European Journal Of Clinical Microbiology & Infectious Diseases: Official Publication Of The European Society Of Clinical Microbiology [serial online]. July 2011;30(7):895-901. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed February 23, 2014.

Antibiotic name Diseases treated m log P Rifapentine Tuberculosis = 4.015

SMILES IUPAC MIC values CC(=O)O[C@H]3[C@H](C)[C@H](O)[C@H]( (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,1 Mycobacterium tuberculosis 0.02 µg/mL C)[C@@H](O)[C@@H](C) \C=C\C=C(\C)C(=O 9E,21Z,26E)-26-{[(4-cyclopentylpiperazin- 1-yl)amino]methylidene}-2,15,17,29- )Nc6c(/C=N/N1CCN(CC1)C2CCCC2)c(O)c5c4 tetrahydroxy-11-methoxy- C(=O)[C@@](C)(O/C=C/[C@H](OC)[C@H]3C 3,7,12,14,16,18,22-heptamethyl-6,23,27- )Oc4c(C)c(O)c5c6O trioxo-8,30-dioxa-24- 4,7 5,28 azatetracyclo[23.3.1.1 .0 ]triaconta- 1(28),2,4,9,19,21,25(29)-heptaen-13-yl acetate Emp. Formula, Molar mass Antibiotic group Trade names C47H64N4O12 , 877.031 g/mol Rifamycins Priftin

Dipole Moment (Debye) Molecular Volume Surface Area 6.45 Debye 879.38 Å3 861.04 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 150.179 Å2 61379-65-5 0.007 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 6 16

References and summary a. MOA : Rifapentine causes bacterial cell death by inhibiting RNA polymerase. (Munsiff, Sonal S., Chrispin Kambili, and Shama Desai Ahuja. "Rifapentine For The Treatment Of Pulmonary Tuberculosis." Clinical Infectious Diseases 43.11 (2006): 1468-1475.)

b. Source : Rifapentine is synthesized from rifampicine. (Sharma, Surendra K, et al. "Rifamycins (Rifampicin, Rifabutin And Rifapentine) Compared To Isoniazid For Preventing Tuberculosis In HIV-Negative People At Risk Of Active TB." Evidence-Based Child Health 9.1 (2014): 169)

c. Cell line Test (MIC) : The efficacy of rifapentine is investigated on the Fa2N-4 cell line. (Mills, Jessica B., et al. "Induction of enzymes and MDR1 using a novel human hepatocyte cell line." Journal of Pharmacology and Experimental Therapeutics 309.1 (2004): 303-309.)

d. Human clinical trials : Rifapentine is evaluated as a preventative drug against active tuberculosis in HIV-negative patients. (Sharma, Surendra K, et al. "Rifamycins (Rifampicin, Rifabutin And Rifapentine) Compared To Isoniazid For Preventing Tuberculosis In HIV-Negative People At Risk Of Active TB." Evidence-Based Child Health 9.1 (2014): 169)

e. Review Article: Rifapentine is evalutated as an antituberculosis drug regiment. (Zumla, A. I., Gillespie, S. H., Hoelscher, M., Philips, P. P. J., Cole, S. T., Abubakar, I., . . . Nunn, A. J. (2014). New antituberculosis drugs, regimens, and adjunct therapies: Needs, advances, and future prospects. The Lancet Infectious Diseases, 14(4), 327-340.)

Antibiotic name Rifaximin Diseases treated Traveler’s m log P Diarrhea 4.417

SMILES IUPAC2S,16Z,18E,20S,21S,22R,23R MIC values< 3.0 µg/ml, clostridium ,24R,25S,26S,27S,28E)- CC(=O)O[C@H]3[C@H](C)[C@H]( difficile infection O)[C@H](C)[C@@H](O)[C@@H](C 5,6,21,23,25-pentahydroxy-27- methoxy-2,4,11,16,20,22,24,26- )\C=C\C=C(\C)C(=O)Nc6c2c(nc1cc(C octamethyl-2,7-(epoxypentadeca- )ccn12)c5c4C(=O)[C@@](C)(O/C=C/ [1,11,13]trienimino)benzofuro [C@H](OC)[C@H]3C)Oc4c(C)c(O)c [4,5-e]pyrido[1,2-a]-benzimida- 5c6O zole-1,15(2H)-dione,25-acetate

Emp. Formula, Molar massC43H51N3O11 , Antibiotic groupNaphthofurans Trade names Xifaxan 785.879 g/mol

Dipole Moment (Debye)4.54 Debye Molecular Volume711.895 Å3 Surface Area477.63 Å2

Surface Area (TPSA) 198.395 Å2 CAS Number80621-81-4 D/V (dipoe moment/volume)0.006 Debye/ Å3

Rotatable # bonds3 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)5 atoms)14

References and summary a. MOA Rifaximin can interfere with transcription by binding the beta-subunit of bacterial RNA polymerase. (Lawrence K., Klee J. Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy 28 (8): 1019–32, 2008)

b. Source Rifaximin derived from Rifamycin SV. (Martinez-Sandoval F, et al., Prevention of travelers' diarrhea with rifaximin in US travelers to Mexico. J Travel Med. 17 (2): 111, 2010)

c. Cell line Test (MIC) : < 3.0 µg/ml of Rifaximin in the treatment of clostridium difficile infection. (Mttila, E., et al., Rifaximin in the treatment of recurrent Clostridium difficile infection. Aliment Pharmacology and Therapeutics. 37 (1); p. 122-128. 2013)

d. Human clinical trials Fifty patients with acute encephalopathy were randomizied to receive 1200 mg/day of rifaximin. (Mas, A., et al., Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. Journal of Hepatology. 38 (1), p. 1155-1164, 2010)

e. Review Article(Layer, P., et al., Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of traveler’s diarrhea. Alimentary Pharmacology & Therapeutics. 43 (2); p. 514-517, 2002) ’

Antibiotic name Diseases treated: infection of the m log P Rosoxacin respiratory tract and urinary tract = 1.298

SMILES IUPAC MIC values CCN1C=C(C(O)=O)C(=O)C2=C1C=C( 1-ethyl-4-oxo-7-(pyridin-4-yl)- β-lactamase producing gonococci C=C2)C1=CC=NC=C1 1,4-dihydroquinoline-3- 0.024 mg/l carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C17H14N2O3 294.30 g/mol Quinolones Eradacil

Dipole Moment (Debye) Molecular Volume Surface Area 6.70 Debye 293.94 Å3 306.37 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 51.386 Å2 40034-42-2 0.023 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 1 5

References and summary a. MOA: Rosoxacin binds to and inhibits the production topoisomerase II and topoisomerase IV enzymes which in turn prevents bacterial DNA replication, transcription, repair, and recombination. (Przybilla, B, et al. "Demonstration Of Quinolone Phototoxicity In Vitro." Dermatologica 181.2 (1990): 98-103)

b. Source: N/A

c. Cell line Test (MIC) : Rosoxacin is used as a base the fluoroquinolone synthesis of 1-(tert-butyl)-6-fluoro-7-(4-hydroxyphenyl)-4- oxo-1,4-dihydroquinoline-3-carboxylic acid and is used against Mycobacterium tuberculosis H37RV. The minimum inhibitory concentration was determined to be 16 µg/mL. (Valentina, Guerrini, et al. "Drug Discovery And Resistance: New Fluoroquinolones Active Against Fluoroquinolones-Resistant Mycobacterium Tuberculosis Strains." Tuberculosis 93.(n.d.): 405-411. ScienceDirect.) d. Human clinical trials : Patients with non-gonococcal urethritis (NGU) were treated with rosoxacin. This trial concluded rosoxacin to be unsuccessful for treatment of NGU. (Hawkins, D A, et al. "Unsuccessful Treatment Of Non-Gonococcal Urethritis With Rosoxacin Provides Information On The Aetiology Of The Disease." Genitourinary Medicine 61.1 (1985): 51)

e. Review Article: This article focuses on the adverse effect of rosoxacin in reference to photosensitivity of the skin. (Nayak, Pragya. "Commonly Used Photosensitizing Medications: Their Adverse Effects And Precautions To Be Considered." International Journal Of Pharmaceutical Sciences Review & Research 4.2 (2010): 135.)

Antibiotic name Diseases treated Poultry m log P = 0.33 Roxarsone disease, blackhead disease

SMILES IUPAC MIC values

Oc1ccc(cc1-n(:o):o)[As](O)(O)=O 4-Hydroxy-3- Campylobacter spp.: MIC50 = 64 µg/ml

nitrobenzenearsonic acid MIC90 = 256 µg/ml

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C6AsNH6O6 Organoarsenic compound Not Found Molar mass: 263.037 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 4.95 Debye 175.06 Å3 116.745 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 123.579 Å2 121-19-7 0.028 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 7 3

References and summary a. MOA Inhibits angiogenesis (Basu, P., Ghosh, RN., Grove, LE., Klei, L., Barchowsky, A., Angiogenic Potential of 3-Nitro-4-Hydroxy Benzene Arsonic Acid (Roxarsone)., Environ Health Perspect., 116(4), 520-523, 2008). 2

b. Source Campylobacter jejuni (Shen, Z., Luangtongkum, T., Qiang, Z., Jeon, B., Wang, L., Zhang, Q., Identification of a Novel Membrane Transporter Mediating Resistance to Organic Arsenic in Campylobacter jejuni., Antimicrob Agents Ch., 58(4), 2137- 13, 2014). 3

c. Cell line Test (MIC) Campylobacter spp.: MIC50 = 64 µg/ml MIC90 = 256 µg/ml (Sapkota, AR., Price, LB., Silbergeld EK., Schwab KJ., Arsenic Resistance in Campylobacter spp. Isolated from Retail Poultry Products., Appl. Environ. Microbiol., 72(4), 3069-3071, 2006). 1

d. Human clinical trials Not Available

e. Review Article 1) Sapkota, AR., Price, LB., Silbergeld EK., Schwab KJ., Arsenic Resistance in Campylobacter spp. Isolated from Retail Poultry Products., Appl. Environ. Microbiol., 72(4), 3069-3071, 2006.

Antibiotic name Diseases treated m log P = 2.774 Roxithromycin Respiratory infections

SMILES IUPAC MIC values O=C3O[C@H](CC)[C@](O)(C)[C@H]( (3R,4S,5S,6R,7R,9R,11S,12R,13S,14R)- H. influenza- 0.5-16 μg/ml O)[C@H](\C(=N\OCOCCOC)[C@H](C) 6-{[(2S,3R,4S,6R)-4-(dimethylamino)- 3-hydroxy-6-methyloxan-2-yl]oxy}-14- C[C@](O)(C)[C@H](O[C@@H]1O[C@ ethyl-7,12,13-trihydroxy-4- H](C)C[C@H](N(C)C)[C@H]1O)[C@H] {[(2R,4R,5S,6S)-5-hydroxy-4-methoxy- ([C@H](O[C@@H]2O[C@H]([C@H](O 4,6-dimethyloxan-2-yl]oxy}- )[C@](OC)(C2)C)C)[C@H]3C)C)C 3,5,7,9,11,13-hexamethyl-10-(2,4,7- trioxa-1-azaoctan-1-ylidene)-1- oxacyclotetradecan-2-one Emp. Formula, Molar mass Antibiotic group Trade names C41H76N2O15, 823.031 g/mol Marcolide Rulid, Surlid, and Coroxin

Dipole Moment (Debye) Molecular Volume Surface Area 8.16 Debye 838.71 Å3 813.21 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 159.142 Å2 80214-83-1 0.0097 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 13 available, attached to O, S, N) atoms) 5 17

References and summary a. MOA Macrolides inhibit protein synthesis. They do this by preventing peptidyltransferase and ribosomal translocation. (Gaynor, M., Macrolide Antibiotics: Binding Site, Mechanism of Action, Resistance, Current Topics in Medicinal Chemistry, Vol. 3, No. 9, p. 949-958, 2003)

b. Source Macrolides are produced by bacteria of the Streptomyces spp. (Xue, Y., et al., A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: Architecture of metabolic diversity, Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 21, p. 12111-12115, 1998)

c. Cell line Test (MIC) Roxithromycin has a MIC of 0.5-16 μg/ml when used on Haemophilus influenza. (Goldstein, F., Emirian, M., and Acar, J., Bacteriostatic and bactericidal activity of azithromycin against Haemophilus influenza, Journal of Antimicrobial Chemotherapy, Vol. 25, p. 25-28, 1990)

d. Human clinical trials Roxithromycin was used in a clinical trial to treat Mediterranean Spotted Fever. (Cascio, A., et al., Efficacy and Safety of Clarithromycin as Treatment for Mediterranean Spotted Fever in Children: A Randomized Controlled Trial, Clinical Infectious Diseases, Vol. 33, Issue 3, p. 409-411, 2001)

e. Review Article A review of Roxithromycin and the eradication of Helicobacter pylori. (Klotz, U., Pharmacokinetic Considerations in the Eradication of Helicobacter Pylori, Clinical Pharmacokinetics, Vol. 38, Issue 3, p. 261, 2000)

Antibiotic name Diseases treated m log P Rufloxacin UTI’s and Infections of the prostate = -0.248

SMILES IUPAC MIC values CN1CCN(CC1)C1=C2SCCN3C=C(C 9-Fluoro-10-(4- Enterobacteriaceae spp.- 0.5-8 µg/ml (O)=O)C(=O)C(C=C1F)=C23 methylpiperazin-1-yl)-7-oxo- Staphylococci spp.- 2-8 µg/ml 2,3-dihydro-7H- [1,4]thiazino[2,3,4- ij]quinoline-6-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C17H18FN3O3S, 363.314 g/mol Quinolone Ruflox, Monos, and Qari

Dipole Moment (Debye) Molecular Volume Surface Area 5.34 Debye 335.37 Å3 346.64 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 54.690 Å2 101363-10-4 0.0159 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 1 6

References and summary a. MOA Quinolones inhibit topoisomerase and gyrase, which results in DNA fragmentation. (Yoshida, H., et al., Mechanism of Action of Quinolones against Escherichia coli DNA Gyrase, Antimicrobial Agents and Chemotherapy, Vol. 37, No. 4, p. 839-845, 1993)

b. Source Derived from quinine, which is isolated from Cinchona bark. (Wyler, D., Fluoroquinolones for Malaria: The Newest Kid on the Block?, Annals of Internal Medicine, Vol. 111, No. 4, p. 269, 1989)

c. Cell line Test (MIC) Rufloxacin was tested on Enterobacteriaceae spp. and Staphylococci spp. the MIC values were 0.5-8 µg/ml and 2-8 µg/ml, respectively. (Mattina, R., Cocuzza, C., Cesan, M., and Bonfiglio, G., In vitro Activity of a New Quinolone, Rufloxacin, against Nosocomial Isolates, Chemotherapy, Vol. 37, No. 4, p. 260-269, 1991) d. Human clinical trials Rufloxacin was compared to Norfloxacin to see which inhibits fecal Escherichia coli more effectively. (Bauer, T., et al., Daily Norfloxacin Is More Effective Than Weekly Rufloxacin in Prevention of Spontaneous Bacterial Peritonitis Recurrence, Digestive Diseases and Sciences, Vol. 47, Issue 6, p. 1356- 1361, 2002)

e. Review Article Review of the of fluoroquinolones and their elimination patterns. ( Turnidge, J., Pharmacokinetics and Pharmacodynamics of Fluoroquinolones, Drugs, Vol. 58, Issue 2, p. 29-36, 1999)

Antibiotic name Diseases treated m log P Silversulfadiazine Burns = -3.022

SMILES IUPAC MIC values

[Ag+].O=S(=O)([N-]c1ncccn1)c2ccc(N)cc2 Silver[(4aminophenyl)sulfonyl](p 32 and 40.2 μg/mL when tested for

yrimidin-2-yl)azanide inhibition against both K. pneumoniae

and E. coli.

Emp. Formula, Molar mass Antibiotic group Trade names

C10H9AgN4O2S, 357.14 g/mol Topical Silvadene

Dipole Moment (Debye) Molecular Volume Surface Area 4.13 Debye 249.36 Åᶾ 80.932 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 100.049 Ų 22199-08-2 0.0166 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA Silver sulfadiazine focues on the cell membrane and inhibition of enzymes. (Hoffmann, Steen. "Silver sulfadiazine: an antibacterial agent for topical use in burns." Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery 18.1 (1984): 119-126.

b. Source The main ingredient in Silver sulfadiazine is Ag (silver). (Fox Jr, C. L. "Topical therapy and the development of silver sulfadiazine." Surgery, gynecology & obstetrics 157.1 (1983): 82-88.

c. Cell line Test (MIC) A cell line test of 32 and 40.2 μg/mL was carried out to test for inhibition against both K. pneumoniae and E. coli. (Shanmugasundaram, N., et al. "Design and delivery of silver sulfadiazine from alginate microspheres‐impregnated collagen scaffold." Journal of Biomedical Materials Research Part B: Applied Biomaterials 77.2 (2006): 378-388.

d. Human clinical trials A human clinical trial was carried out to test the efficacy of Biobrane versus Silversulfadiazine in pediatric burns with second-degree. (Barret, Juan P., et al. "Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns." Plastic and reconstructive surgery 105.1 (2000): 62-65.

e. Review Article This article reviews Silversulfadiazine and how it treats burn wounds. (Fuller, Frederick W., Margarete Parrish, and Francis C. Nance. "A review of the dosimetry of 1% silver sulfadiazine cream in burn wound treatment." Journal of Burn Care & Research 15.3 (1994): 213-223.

A review of Silversulfadiazine cream and how it prevents transurethral catheter-associated bacteriuria. (Huth, Thomas S., et al. "Randomized trial of meatal care with silver sulfadiazine cream for the prevention of catheter- associated bacteriuria." Journal of Infectious Diseases 165.1 (1992): 14-18.

Antibiotic nameSitafloxacin Diseases treatedBuruli ulcer m log P -0.191

SMILES F[C@H]5C[C@H]5N2/C=C(/C(=O) IUPAC 7-[(4S)-4-Amino-6- MIC values1 µg/ml, enterobacterial O)C(=O)c1cc(F)c(c(Cl)c12)N4C[C@@H](N) azaspiro[2.4]heptan-6-yl]-8- species C3(CC3)C4 chloro-6-fluoro-1-[(2S)-2- fluorocyclopropyl]-4- oxoquinoline-3-carboxylic acid

Emp. Formula, Molar mass Antibiotic groupFourth Trade namesGracevit

C19H18ClF2N3O3 , 409.81 g/mol Generation Quinolones

Dipole Moment (Debye)5.43 Debye Molecular Volume325.328 Å3 Surface Area493.11 Å2

Surface Area (TPSA)88.565 Å2 CAS Number127254-12-0 D/V (dipoe moment/volume)0.017 Debye/ Å3

Rotatable # bonds3 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)3 atoms)6

References and summary a. MOA Inhibits the topoisomerase II ligase domain, leaving the two nuclease domain to be intact. This results in DNA fragmentation via the nucleasic activity of the intact enzyme domains. (Tanaka M, Hoshino K. Ishida H. Sat0 K, Hayakawa I. Osada Y . Antimicrobial activity of DV-7751a, a new fluoroquinolone. Antinricrob Ayents Chemother; 37 : 21 12-21 18, 1993)

b. SourceSitafloxacin derives from Nalidixic acid. (Piddock LJV. New quinolones and gram-positive bacteria. Antimicrob Agenrs Chemother; 38 : 163- 169, 1994)

c. Cell line Test (MIC) MIC=1 µg/ml was 96.9 % effective against enterobacterial species. (Sato, K., Hoshino, K., Tanaka, M, Hayakawa I., Osada Y. Antimicrobial activity of DU-6859. a new potent fluoroquinolone, against clinical isolates. Anrimicrob Agents Chemother ;36:1491-1498, 1992)

d. Human clinicalThis trial was carried out to determine the activity of 4-quinolones against Pseudomonas aeruginosa in humans. trials (Morrissey I, Smith JT. The activity of 4-quinolones against Pseudomonas aeruginosa. Arzneim- Forschl Drug Res; 44: 1157-1161, 1994)

e. Review Article Anderson, DL. Sitafloxacin hydrate for bacterial infections.Drugs Today 44 (7): 489–50, 2008.

Antibiotic name Diseases treated m log P Sparfloxacin Community acquired pneumoniae = 1.628

SMILES IUPAC MIC values C[C@@H]1CN(C[C@@H](N1)C)c2c(c(c3c( 5-Amino-1-cyclopropyl-7- Streptococcus pneumoniae 16 µg/ml c2F)n(cc(c3=O)C(=O)O)C4CC4)N)F [(3R,5S)3,5-dimethylpiperazin-1- yl]-6,8-difluoro-4-oxo-quinoline- 3-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names rd C19H22F2N4O3 392.41 g/mol Quinolone (3 generation) Zagam

Dipole Moment (Debye) Molecular Volume Surface Area 5.48 Debye 369.91 Å3 383.89 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 76.864 Å2 110871-86-8 0.015 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 4 9

References and summary a. MOA: Sparfloxacin inhibits the bacterial DNA topoisomerase IV enzyme which in turn inhibits DNA replication and transcription. (Piddock, L J, and M Zhu. "Mechanism Of Action Of Sparfloxacin Against And Mechanism Of Resistance In Gram-Negative And Gram-Positive Bacteria." Antimicrobial Agents And Chemotherapy 35.11 (1991): 2423-2427)

b. Source: N/A

c. Cell line Test (MIC): This cell line tests the effectiveness of sparfloxacin against resistance in gram-negative and gram-positive bacteria. The test recommended a sparfloxacin concentration of > 1µg/ml for the one step mutations that occur in E. cloacae, S. marcescens, and K. pneumonia. (Piddock, L J, and M Zhu. "Mechanism Of Action Of Sparfloxacin Against And Mechanism Of Resistance In Gram-Negative And Gram-Positive Bacteria." Antimicrobial Agents And Chemotherapy 35.11 (1991): 2423-2427) d. Human clinical trials : Sparfloxacin is adminisitered to patients with lepromatous leprosy in order to determine if the drug is bacteriacidal for Mycobacterium leprae. (Chan, Gertude P., et al. “Clinical trail of sparfloxacin for lepromatous leprosy.” Antimicrobial agents and chemotherapy 38.1 (1994): 61-65)

e. Review Article: This article discusses the neurological and psychiatric adverse drug reactions of sparfloxacin and other quinolones. (Tomé, Ana M.Filipe, Augusto. "Quinolones: Review Of Psychiatric And Neurological Adverse Reactions." Drug Safety 34.6 (2011): 465.)

Antibiotic name Spectinomycin Diseases treated m log P -2.731 Gonorrhea

SMILES IUPAC MIC values C[C@@H]1CC(=O)[C@]2([C@@H](O1)O[ (1R,3S,5R,8R,10R,11S,12S,13R,1 N. gonorrhoeae, 16 µg/mL C@@H]3[C@H]([C@@H]([C@@H]([C@ 4S)-8,12,14-trihydroxy-5-methyl- @H]([C@H]3O2)NC)O)NC)O)O 11,13-bis(methylamino)-2,4,9- trioxatricyclo[8.4.0.03,8]tetradec an-7-one

Emp. Formula, Molar mass Antibiotic group Trade names C14H24N2O7, 332.35 g/mol Aminocyclitol Trobicin

Dipole Moment (Debye) Molecular Volume Surface Area 2.55 Debye 312.16 Å3 336.15 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 129.511 Å2 1695-77-8 0.0082 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 5 9

References and summary a. MOA Spectinomycin binds to bacterial ribosomes and interrupts proteien sysnthesis. Specifically it binds to ribosomal subunits 30S and 16s. A mutation in gonorrhea and the 16s subunit has been idedentified and resistance has formed in certain strains. (Unemo, Magnus et. al. Neisseria gonorrhoeae Strain with High-Level Resistance to Spectinomycin Due to a Novel Resistance Mechanism (Mutated Ribosomal Protein S5) Verified in Norway. Antimicrobial Agents and Chemotherapy, Vol. 57 No. 2, 1057–1061, 2013.)

b. Source Spectinomycin is derived from Streptomyces spectabilis. (Duncan, C.W., W.R. Holder, D.P. Roberts and J.M. Knox. “Treatment of Gonorrhea with Spectinomycin Hydrochloride: Comparison with Standard Penicillin Schedules .” Antimicrobial Agents and Chemotherapy, Mar, 210-214, 1972.)

c. Cell line Test (MIC) A group of researchers assessed the susceptibly of N. Gonorrhoeae to different antibiotics because of feared resistance. They found spectinomycin to still be somewhat effective. (Ito, Masayasu et. al. “Remarkable Increase in Central Japan in 2001-2002 of Neisseria gonorrhoeae Decreased Susceptibility to Penicillin, Tetracycline, Oral Isolates with Cephalosporins, and Fluoroquinolones.” Antimicrobial Agents and Chemotherapy, Vol. 48, No. 8, 3185-3187, 2004.) d. Human clinical trials In 1971-72 clinical trials of spectinomycin were conducted in the treatment of gonorrhea. Results showed a 99.6 percent cure rate and it was suggested that the drug be used for patients with aversions to penicillin. (Finger, Alan H. “Spectinomycin in the treatment of gonorrhoea in females and males.” British Journal of Venereal Diseases, Vol. 51, 38-40, 1975.)

e. Review Article (Galimand, Marc, Guy Gerbaud, and Patrice Courvalin. “Spectinomycin Resistance in Neisseria spp. Due to Mutations in 16S rRNA.” Antimicrobial Agents and Chemotherapy, Vol. 44, No. 5, 1365–1366 2000.)

Antibiotic name Diseases treated Toxoplasmosis, m log P = 2.297 Spiramycin Infections of the soft tissues

SMILES IUPAC MIC values O=CCC4C(OC2OC(C(OC1OC(C)C(O)C(O)(C) (4R,5S,6R,7R,9R,10R,11E,13E,16R)-10- Streptococcus uberis: 8 µg/ml C1)C(N(C)C)C2O)C)C(OC)C(O)CC(=O)OC(C) {[(2R,5S,6R)-5-(dimethylamino)-6- Staphylococcus aureus: 15.6 µg/ml and H methyltetrahydro-2 -pyran-2-yl]oxy}- C\C=C\C=C\C(OC3OC(C)C(N(C)C)CC3)C(C) 9,16-dimethyl-5-methoxy-2-oxo-7-(2- 23.4 µg/ml C4 oxoethyl)oxacyclohexadeca-11,13-dien- 6-yl 3,6-dideoxy-4-O-(2,6-dideoxy-3-C- methyl-α-L-ribo-hexopyranosyl)-3- (dimethylamino)-α-D-glucopyranoside Emp. Formula, Molar mass Antibiotic group Trade names Macrolide Antibiotic Rovamycine, Toxocare, Zyramycin Emp. Formula: C43H74N2O14 Molar mass: 843.065 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 6.29 Debye 870.13 Å3 155.266 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 195.402 Å2 8025-81-8 0.007 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 11 available, attached to O, S, N) atoms) 4 2

References and summary a. MOA Spiramycin inhibits protein synthesis of bacteria. (Brisson-Noël, A., Trieu-Cuot, P., Courvalin P., Mechanism of action of spiramycin and other macrolides., J Antimicrob Chemother., 22, 13-23, 1988). 1

b. Source Streptomyces ambofaciens (Karray, F., Darbon, E., Nguyen, HC., Gagnat, J., Pernodet, J., Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens., J Bacteriol., 192(21), 5813-5821, 2010). 4

c. Cell line Test (MIC) Streptococcus uberis: 8 µg/ml (Achard, A., Guérin-Faublée, V., Pichereau, V., Villers, C., Leclercq, R., Emergence of Macrolide Resistance Gene mph(B) in Streptococcus uberis and Cooperative Effects with rdmC-Like Gene., Antimicrob. Agents Chemother., 52(8), 2767-2770, 2008). 2 Staphylococcus aureus: 15.6 µg/ml and 23.4 µg/ml (Esimone, CO., Iroha, IR., Okeh, OC., Ude, IG., Adikwu, MU., In vitro interaction of ampicillin with ciprofloxacin or spiramycin as determined by the decimal assay for additivity technique., Nigerian Journal of Health and Biomedical Sciences., 5(1), 12-16, 2006). 3

d. Human clinical trials Condition: (Cryptosporidiosis, HIV infections) Intervention: (Drug: Spiramycin), Phase 1.

e. Review Article 1) Brisson-Noël, A., Trieu-Cuot, P., Courvalin P., Mechanism of action of spiramycin and other macrolides., J Antimicrob Chemother., 22, 13-23, 1988. 2) Achard, A., Guérin-Faublée, V., Pichereau, V., Villers, C., Leclercq, R., Emergence of Macrolide Resistance Gene mph(B) in Streptococcus uberis and Cooperative Effects with rdmC-Like Gene., Antimicrob. Agents Chemother., 52(8), 2767-2770, 2008. 3) Esimone, CO., Iroha, IR., Okeh, OC., Ude, IG., Adikwu, MU., In vitro interaction of ampicillin with ciprofloxacin or spiramycin as determined by the decimal assay for additivity technique., Nigerian Journal of Health and Biomedical Sciences., 5(1), 12-16, 2006. 4) Karray, F., Darbon, E., Nguyen, HC., Gagnat, J., Pernodet, J., Regulation of the Biosynthesis of the Macrolide Antibiotic Spiramycin in Streptomyces ambofaciens., J Bacteriol., 192(21), 5813-5821, 2010.

Antibiotic name Streptomycin Diseases treated Tuberculosis m log P -5.35

• SMILESC[C@H]1[C@@]([C@H]([C IUPAC5-(2,4-diguanidino- MIC values>50,000 µg/ml against @@H](O1)O[C@@H]2[C@H]([C 3,5,6-trihydroxy-cyclohexoxy)- 4- Enterococci @@H]([C@H]([C@@H]([C@H]2O [4,5-dihydroxy-6-(hydroxymethyl) )O)N=C(N)N)O)N=C(N)N)O[C@H] -3-methylamino-tetrahydropyran-2- 3[C@H]([C@@H]([C@H]([C@@H yl] oxy-3-hydroxy-2-methyl -tetrahydrofuran-3-carbaldehyde ](O3)CO)O)O)NC)(C=O)O

Emp. Formula, Molar mass Antibiotic groupAminoglycoside Trade namesGeneric only C21H39N7O12 581.6 g/mol

Dipole Moment (Debye)0.9 Debye Molecular Volume477.11 Å3 Surface Area509.20 Å2

Surface Area (TPSA)226.60 Å2 CAS Number57-92-1 D/V (dipoe moment/volume)0.00189 Debye/ Å3

Rotatable # bonds9 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)19 atoms)16

References and summary a. MOA Since streptomycin is a protein synthesis inhibitor, it binds to the small S16 rRNA of the 30S subunit of the bacterial ribosome which interfers with the binding of formyl-methionyl-tRNA to the 30S subunit which leads to codon misreading, eventual inhibition of protein synthesis and lastly death of microbial cells (Sharma D, Cukras AR, Rogers EJ, Southworth DR, Green R (7 December 2007). "Mutational analysis of S12 protein and implications for the accuracy of decoding by the ribosome". Journal of Molecular Biology 374 (4): 1065–76.)

b. Source Being a bactericidal antibiotic, it is derived from the actinobacterium Streptomyces griseus. (Singh B, Mitchison DA (16 January 1954). "Bactericidal Activity of Streptomycin and Isoniazid Against Tubercle Bacilli". British Medical Journal 1 (4854): 130–132.)

c. Cell line Test The action of penicillin in combination with gentamicin against enterococci was studied. The susceptibility to penicillin, gentamicin, and streptomycin was examined using one hundred strains of enterococci, 14 of which were recovered from blood cultures of patients with endocarditis. All strains were inhibited by ≤50 µg of gentamicin/ml. The majority were inhibited by ≤78 µg of streptomycin/ml, but 13 strains were not inhibited by 50,000 µg/ml. Thirty-three strains were studied for synergism of combinations of antibiotics. A combination of 20 µg of penicillin and 4 µg of gentamicin/ml was synergistic against all 33 strains, while 20 µg of penicillin combined with 20 µg of streptomycin/ml was synergistic against only 20 of the 33 strains. The minimal inhibitory concentration of streptomycin for four of these 20 strains was more than 50,000 µg/m (Watanakunakorn, C. 1971. “Penicillin combined with Gentamicin or Streptomycin: Synergism against Enterococci”. The Journal Of Infectious Diseases (124). 581-585 l (MIC) d. Human clinical In order to determine pyrazinamide (PZA) monoresistance in clinical isolates of My cob acterium tuberculosis complex (MTBC) isolated in hospitals in and around İzmir, a study was performed between 2004 and 2009 with 150 streptomycin, isoniazid, rifampicin, and ethambutol susceptible MTBC clinical strains isolated in the university hospitals of İzmir and Manisa. The BACTEC 460 TB test determined by the PZA susceptibility of the isolates. The resistance to PZA which was present in 5 (3.3%) of the 150 MTBC isolates susceptible to all primary drugs except PZA was indicated by the results. It is concluded that it is not essential to perform PZA susceptibility tests routinely along with other primary drugs due to the low PZA monoresistance level in our region (KALIR, N, ÖZKÜTÜK, A, ESEN, N, & ÖZKÜTÜK, N 2013, 'Pyrazinamide monoresistance in clinical isolates', Turkish Journal Of Medical Sciences, 43, 1, pp. 163-167) trials e. Review Article In this study, the microbiota present in the faeces of 15- and 46-week-old egg laying hens before and after tetracycline or streptomycin therapy was characterized. The changes in microbiota composition that the antibiotic therapy induced were rapid and dramatic and only representatives of the genera Enterococcus. Also, Escherichia responded increasingly to the therapy with both antibiotics in both experiments (Videnska, P, Faldynova, M, Juricova, H, Babak, V, Sisak, F, Havlickova, H, & Rychlik, I 2013, 'Chicken faecal microbiota and disturbances induced by single or repeated therapy with tetracycline and streptomycin', BMC Veterinary Research, 9, p. 30)

Antibiotic name Sulfacetamide Diseases treated acne and m log P -0.557 seborrheic dermatitis

SMILES O=S(=O)(c1ccc(N)cc1)NC(=O)C IUPAC N-[(4- MIC values 0.3 -0.5 lug/mL. against aminophenyl)sulfonyl]acetamide Aspergillus and Candida spp.

Emp. Formula, Molar mass C H N O S Antibiotic group sulfonamide Trade names Klaron or Ovace 8 10 2 3 antibiotic

Dipole Moment (Debye) 5.82 Debye Molecular Volume 195.55 Ǻ3 Surface Area 228.91 Ǻ2

Surface Area (TPSA) 89.263 CAS Number 144-80-9 D/V (dipoe moment/volume) 0.0299 Debye/ Ǻ3

Rotatable # bonds 2 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 3 atoms) 5

References and summary a. MOA Antibacterial sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis. (M. Madigan, J. Martinko, D. Stahl, D. Clark, Brock. 2012. Biology of Microorganisms (13th ed.), Pearson Educationp. 797)

b. Source The original antibacterial sulfonamides (sometimes called sulfa drugs or sulpha drugs) are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity (Henry, R. J. 1943. "The Mode of Action of Sulfonamides". Bacteriological reviews (4): 175–262)

c. Cell line Test An in vitro assay of teratogenesis has been developed that utilizes Drosophila embryonic cell cultures. The endpoint selected in assessing the teratogenic potential of any substance involves detection of interference with normal muscle and/or neuron differentiation. In the validation phase of this project, 100 chemicals were tested. (Bournias‐Vardiabasis, N., Teplitz, R. L., Chernoff, G. F., & Seecof, R. L. 1983. Detection of teratogens in the Drosophila embryonic cell culture test: assay of 100 chemicals. Teratology, 28(1), 109-122) (MIC) d. Human clinical Trimethoprim in combination with sulfacetamide and polymyxin B and also in combination with polymyxin B alone (without the sulfacetamide) were studied to determine the efficacy and safety of these new antibiotic combinations in the eyes of patients with bacterial conjunctivitis or blepharitis. (Lamberts, D. W., Buka, T. H. E. O. D. O. R. E., & Knowlton, G. M. 1984. Clinical evaluation of trimethoprim-containing ophthalmic solutions in humans. American journal of ophthalmology, 98(1), 11-16) trials

e. Review Article Acute bacterial conjunctivitis is frequently a self-limiting condition but the use of antibiotics is associated with significantly improved rates of early clinical remission, and early and late microbiological remission. (Sheikh, A., & Hurwitz, B. 2001. Topical antibiotics for acute bacterial conjunctivitis: a systematic review. The British Journal of General Practice,51(467), 473.)

Antibiotic name Diseases treated m log P Sulfadiazine urinary tract infections, malaria, cear infections =-0.044

SMILES IUPAC MIC values c1(S(Nc2ncccn2)(=O)=O)ccc(N)cc1 4-amino-N-pyrimidin- 2-yl- 0.05-20 mg/ml,

benzenesulfonamide

Emp. Formula, Molar mass Antibiotic group Trade names

C10H10N4O2S, 250.278 g/mol Sulfonamide Lantrisul, Neotrizine

Dipole Moment (Debye) Molecular Volume Surface Area 6.87 Debye 228.61 Å3 258.79 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 97.976 Å2 68-35-9 0.03 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA The mechanism of action was determined to be the inhibition of folic acid production, which is necessary for the growth of bacteria. (Jung, W., Antibacterial Activity and Mechanism of Action of the Silver Ion in Staphylococcus aureus and Escherichia coli, App. Environ. Mirob., 80(8), p. 2171-2178, 2008)

b. Source Sulfadiazine was derived from synthetic antimicrobial agents that contain the sulfonamide group. (Chang, H., et al, Simultaneous analysis of 16 sulfonamide and trimethoprim antibiotics in environmental waters by liquid chromatography-electrospray tandem mass spectrometry, J. Chrom. 1190, p. 390-393, 2008)

c. Cell line Test (MIC) 0.05-20 mg/ml, Neisseria meningitidis (Wiggins, G., et al, Susceptibility of Neisseria meningitidis Strains from the Civilian Population to Sulfadiazine, Penicillin, and Rifampin, App. Environ. Microb., 20(6), p. 893-898, 1970)

d. Human clinical trials 11 patients were treated to test the effectiveness of silver sulfadiazine against ulcers. (Kucan, J., et al, Comparison of silver sulfadiazine, povidone-iodine and physiologic saline in the treatment of chronic pressure ulcers, J. Am. Geriat. Soc., 29(5), p. 232-235, 1981)

e. Review Article Silver sulfadiazine was discussed as a possible treatment option for burn wounds. (Fox, C. et al, Silver Sulfadiazine- A New Topical, JAMA, 96(2), p. 184-188, 1968)

Antibiotic name Diseases treated m log P Urinary tract infections = 0.21

SMILES IUPAC MIC values

O=S(=O)(Nc1nnc(s1)C)c2ccc(N)cc2 4-amino-N-(5-methyl-1,3,4- 128 μg/mL when tested for inhibition

thiadiazol-2-yl)- against Escherichia coli.

benzenesulfonamide

Emp. Formula, Molar mass Antibiotic group Trade names C9H10N4O2S2, 270.333 g/mol Sulfonamide antibiotic. Thiosulfil Forte

Dipole Moment (Debye) Molecular Volume Surface Area 5.21 Debye 227.16 Åᶾ 251.25 Ų

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 97.976 Ų 144-82-1 0.023 Debye/Åᶾ

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 2 5

References and summary a. MOA The mechanism of action of Sulfamethizole is that it inhinits a bacterial enzyme which is dihydropteroate synthetase. (Borrás, Elisa, et al. "Coordination chemistry of sulfamethizole: crystal structures of [Cu (sulfamethizolate) 2 (py) 2 (OH 2)]· H 2O,[M (sulfamethizolate) 2 (py) 2 (OH 2) 2][M= Co and Ni] and {Cu (sulfamethizolate) 2 (dmf) 2}∞." Polyhedron 19.15 (2000): 1859-1866.

b. Source Sulfamethizole is a sulfonamide antibiotic, which is also called a sulfa drug. (Weidner‐Wells, Michele A., and Mark J. Macielag. "Antibacterial Agents, Sulfonamides." Kirk-Othmer Encyclopedia of Chemical Technology (2003).

c. Cell line Test (MIC) A cell line test of 128 μg/mL was carried out to test for inhibition against Escherichia coli. (Kerrn, M. B., N. Frimodt- Møller, and F. Espersen. "Effects of sulfamethizole and amdinocillin against Escherichia coli strains (with various susceptibilities) in an ascending urinary tract infection mouse model." Antimicrobial agents and chemotherapy 47.3 (2003): 1002-1009. d. Human clinical trials A human clinical trial was carried out to determine the efficacy of Sulfamethizole and trimethoprim to treat a case of colonic malacoplakia. (Christensen, M., S. Knuhtsen, and E. Knudsen. "[Colonic malacoplakia treated with sulfamethizole and trimethoprim]." Ugeskrift for laeger 173.7 (2011): 509-510.

e. Review Article Sulfamethizole promises antimicrobial and antifungal activity against fungi. (Petrikaitė, Vilma, Eduardas Tarasevičius, and Alvydas Pavilonis. "New thiazolidones-4 with sulfamethizole-2 substituent as potential antifungal and antimicrobial preparations." Biologija 3 (2007).

This article refers to how Sulfamethizole is determined. (Raviolo, Mónica Ana, et al. "Determination of sulfonamides in milk after precolumn derivatisation by micellar liquid chromatography." Analytica chimica acta 593.2 (2007): 152-156.

Antibiotic name Diseases treated Staphylococcus m log P 0.609 Sulfamethoxazole aureus, H. Influenzae, E.Coli

SMILES IUPAC MIC values CC1=CC(=NO1)NS(=O)(=O)C2=CC=C 4-amino-N-(5-methylisoxazol-3- .0.06 µg/mL Enterococcus spp. (C=C2)N yl)-benzenesulfonamide

Emp. Formula, Molar mass Antibiotic group Trade names C10H11N3O3S; 253.279 g/mol Sulfonamide Bactrim

Dipole Moment (Debye) Molecular Volume Surface Area 5.84 Debye 230.70Å3 263.81 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 98.224 Å2 723-46-6 0.025 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 6 3

References and summary a. MOA Sulfamethoxazole inhibits the production of intermediary dihydrofolic acid in bacteria. Dihydrofolic acid is a precursor to tetrahydrofolic acid and tetrahydrofolic acid is integral for bacterial DNA synthesis resulting in a bactericidal effect. (Masters P.A, O'Bryan T.A, Zurlo J, Miller D.Q, Joshi N. Trimethoprim-Sulfamethoxazole Revisited Arch Intern Med. 163(4), 402-410, 2003.)

2 b. Source Sulfamethoxazole is a synthetic sulfonamide. (Heinkele , G. and Murdter, T.E. Synthesis of [ H3]-labelled sulfamethoxazole and its main urinary metabolites. Journal of Labelled Compounds and Radiopharmaceuticals. 50, 656–659, 2007).

c. Cell line Test (MIC) In a study done on urinary tract infections, bacterial isolates were tested against Trimethoprim- Saulfamethoxazole; commonly abbreviated SXT. Strains of isolates included E.coli , enterococcus, K. pneumonia, P. mirabilis, and S. saprophyticus; Two thousand different isolates in total. SXT had a median MIC value of 0.12 µg/mL against this bacterial array. (Zahnel, George G. et al. A Canadian National Surveillance Study of Urinary Tract Isolates from Outpatients: Comparison of the Activities of Trimethoprim-Sulfamethoxazole, Ampicillin, Mecillinam, Nitrofurantoin, and Ciprofloxacin. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 1089–1092, 2000) d. Human clinical trials A clinical trial was conducted in 1991 to assess the effectiveness and toxicity of trimethoprim- sulfamethoxazole in treating Pneumocystis carinii pneumonia in HIV patients. The study showed trimethoprim- sulfamethoxazole to be an effective method of treatment with low side effects in the HIV paitients. (D.S. Stein, R. C. Stevens, D. Terry, S. C. Laizure, S. Palte, D. J. Lancaster, J.J. Weems and C.L. William. Use of low-dose trimethoprim-sulfamethoxazole thrice weekly for primary and secondary prophylaxis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept., 1705-1709, 1991). e. Review Article (Norman Markowitz, Edward L. Quinn, Louis D. Saravolatz. Trimethoprim-Sulfamethoxazole Compared with Vancomycin for the Treatment of Staphylococcus aureus Infection. Annals of Internal Medicine. 117(5), 390-398, 1992).

Antibiotic name Diseases treated m log P Sulfanilamide Streptococcal infections, Leprosy =-0.293

SMILES IUPAC MIC values O=S(=O)(c1ccc(N)cc1)N 4-aminobenzenesulfonamide 500 µg/mL, Bacillus subtilis

Emp. Formula, Molar mass Antibiotic group Trade names C6H8N2O2S, 172.20 g/mol Sulfonamides AVC

Dipole Moment (Debye) Molecular Volume Surface Area 5.82 Debyes 153.65 Å3 183.36 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 86.188 Å2 63-74-1 0.0379 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 1 available, attached to O, S, N) atoms) 4 4

References and summary a. MOA: Sulfanilamide inhibits the enzyme PABA which leads to the inhibition of folic acid synthesis. [Cohen, L., Cluff, L., The sulfonamides, Am. J. Nursing, 61(6), pp. 54-58, 1961].

b. Source: Sulfanilamide is a synthetic antibiotic like the other sulfonamides. [Cohen, L., Cluff, L., The sulfonamides, Am. J. Nursing, 61(6), pp. 54-58, 1961].

c. Cell line Test (MIC): In this study, the sulfanilamide resistance gene was introduced into Bacillus subtilis via a plasmid. Bacillus subtilis strains with and without the sulfanilamide resistance gene plasmid. The MIC value of one of the strains was 500 µg/mL. [McDonald, K., Burke, W., Cloning of the Bacillus subtilis sulfanilamide resistance gene in Bacillus subtilis, J. Bacteriol., 149(1), pp. 391-394, 1982].

d. Human clinical trials: Sulfanilamide is used to treat patients with leprosy at the United States Marine Hospital. [Faget, G., Johansen, F., Sulfanilamide in the treatment of leprosy, Public Health Reports, 121(supplement), pp. 221-223, 2006]

e. Review Article: In this study, several hypotheses concerning the mode of action for sulfanilamide. [Long, P., The mode of action of sulfanilamide, Sigma Xi, 29(3/4), pp. 149-169, 1941].

Antibiotic name Diseases treated: Rheumatiod m log P Sulfasalazine arthritis, Crohn’s disease, ulcerative = 3.905

SMILES IUPAC MIC values O=S(=O)(Nc1ccccn1)c3ccc(/N=N/c2cc(C(O 2-hydroxy-5-[(E)-2-{4-[(pyridin-2- Y. enterocolitica > 1600 µg/mL. )=O)c(O)cc2)cc3 yl)sulfamoyl]phenyl}diazen-1- E. coli > 1600 µg/mL. yl]benzoic acid

Emp. Formula, Molar mass Antibiotic group Trade names C18H14N4O5S , 398.394 g/mol Sulfonamide Azulfidine

Dipole Moment (Debye) Molecular Volume Surface Area 0.94 Debye 361.66 Å3 392.53 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 117.643 Å2 599-79-1 0.003 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 10

References and summary a. MOA : The mechanism for sulfasalazine has yet to be determined. In relation to treatment for inflammatory bowel disease (IBD), it is believed that sulfasalazine metabolite 5-aminosalicylic acid (5-ASA) impacts IBD treatment via nuclear factor-kappaB inhibition. (Cipolla, Giovanna, et al. "Nonsteroidal Anti-Inflammatory Drugs And Inflammatory Bowel Disease: Current Perspectives." Pharmacological Research 46.1 (n.d.): 1-6.)

b. Source : Sulfasalazine is derived from mesalazine. (Schroeder, K. W. "Role Of Mesalazine In Acute And Long-Term Treatment Of Ulcerative Colitis And Its Complications." Scandinavian Journal Of Gastroenterology. Supplement 37.(2002): 42.)

c. Cell line Test (MIC) : The efficacy sulfasalazine and its derivatives 5-ASA and were tested in vitro against diarrhea producing gram negative enteric bacteria including Y. enterocolitica, and E. coli . All strains were found to be resistant to both sulfasalazine and 5-ASA even with concentrations of 1600 µg/mL. (Andreasen, J J, L P Andersen, and S H Hartzen. "In Vitro Susceptibility Of Diarrhoea Producing Gram Negative Enteric Bacteria To Sulfasalazine, 5-Aminosalicylic Acid, Sulfapyridine And Four Quinolones. Brief Report." APMIS: Acta Pathologica, Microbiologica, Et Immunologica Scandinavica 96.6 (1988): 568-570.) d. Human clinical trials : The purpose of this clinical trail was to evaluate the efficacy of sulfasalazine in patients with antihistamine refractory chronic idiopathic urticarial (CIU), a recalcitrant skin disease. As a result of the study ranging from October 2007 to March 2012, sulfasalazine was determined to be highly effective when treating patients with CIU. (Orden, Roy, Anthony, Hersha Timble, and Sarbjit, S Saini. "Efficacy And Safety Of Sulfasalazine In Patients With Chronic Idiopathic Urticaria." Annals Of Allergy, Asthma & Immunology 112.1 (2014): 64-70.)

e. Review Article : This article reviews the mode of action and delivery of 5-aminosalicyclic acid (5-ASA) a sulfasalazine derivative hypothesized to act as a part of sulfasalazine’s mechanism of action by activate nuclear receptors involved in inflammation control, cell proliferation, as well as cell aptoss and metabolic function. (DESREUMAUX, P., and S. GHOSH. "Review Article: Mode Of Action And Delivery Of 5-Aminosalicylic Acid – New Evidence." Alimentary Pharmacology & Therapeutics 24.(2006): 2-9.)

Antibiotic name Diseases treated m log P Sulfisoxazole Malaria, Trachoma =0.986

SMILES IUPAC MIC values CC1=C(ON=C1C)NS(=O)(=O)C2=CC=C(C=C 4-amino-N-(3,4-dimethyl-1,2- 1 µg/mL, Neisseria meningitidis 2)N oxazol-5-yl)benzenesulfonamide

Emp. Formula, Molar mass Antibiotic group Trade names C11H13N3O3S, 267.309 g/mol Sulfonamides Gantrisin

Dipole Moment (Debye) Molecular Volume Surface Area 6.14 Debyes 248.38 Å3 281.91 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 98.224 Å2 127-69-5 0.0247 Debyes/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA: Sulfisoxazole inhibits folic acid synthesis which ultimately inhibits DNA synthesis. [Fiebelkorn, K., Crawford, S., Jorgensen, J., Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitides clinical isolates from five countries, Antimicrob. Ag. Chemother., 49(2), pp. 536-540, 2005].

b. Source: Sulfisoxazole is a synthetic antibiotic. [Dragostin, O., Lupascu, F., Vasile, C., Mares, M., Nastasa, V., Moraru, R., Pieptu, D., Profire, L., Molecules, 18(1), pp. 4140-4157, 2013].

c. Cell line Test (MIC): Sulfisoxazole was shown to inhibit the growth of Neisseria meningitidis at a minimal concentration of 1 µg/mL for a majority of the isolates. [Fiebelkorn, K., Crawford, S., Jorgensen, J., Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitides clinical isolates from five countries, Antimicrob. Ag. Chemother., 49(2), pp. 536-540, 2005].

d. Human clinical trials: In this study, Sulfisoxazole was used to treat patients with otitis media at Wilford Hall US Air Force Medical Center. [Liston, T., Foshee, W., Pierson, W., Sulfisoxazole chemoprophylaxis for frequent otitis media, Ped., 71 (4), pp. 524-530, 1983].

e. Review Article: In this article, Sulfisoxazole’s use as a treatment for urinary tract infections in children is discussed. [Williams, G., Lee, A., Craig, J., Antibiotics for the prevention of urinary tract infection in children; a systematic review of randomized controlled trials, J. Ped., 138(6), pp. 868-874, 2001].

Antibiotic name Torezolid Diseases treated complicated m log P 1.514 skin and skin-structure infections

SMILES IUPAC (5R)-3-{3-fluoro-4-[6-(2- MIC values ≤4 mg/L and ≤2 mg/L against O=C4O[C@H](CN4c3cc(F)c(c1ccc(nc1)c2n methyl - 2 H-tetrazol-5-yl)pyridin- a collection of linezolid-resistant n(nn2)C)cc3)CO 3-yl]phenyl}-5-(hydroxymethyl)- staphylococci

1,3-oxazolidin-2-one

Emp. Formula, Molar mass C H FN O Antibiotic group oxazolidinone Trade names N/A 17 15 6 3 370.338 g/mol

Dipole Moment (Debye) 5.57 Debye Molecular Volume 319.70 Ǻ3 Surface Area 342.78 Ǻ3

Surface Area (TPSA) 106.273 Ǻ3 CAS Number 856866-72-3 D/V (dipoe moment/volume) 0.0174 Debye /Ǻ3

Rotatable # bonds 4 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 9 atoms) 1

References and summary a. MOA acts by inhibiting protein synthesis and has broad activity against Gram-positive pathogens, including strains that are resistant to linezolid. (Kanafani, Z. A., & Corey, G. R. 2012. Tedizolid (TR-701): a new oxazolidinone with enhanced potency. Expert opinion on investigational drugs, 21: 515-522.)

b. Source Tedizolid is a new oxazolidinone prodrug that is transformed in the serum into the active drug tedizolid. (Kanafani, Z. A., & Corey, G. R. 2012. Tedizolid (TR-701): a new oxazolidinone with enhanced potency. Expert opinion on investigational drugs, 21: 515-522.)

c. Cell line Test The majority of the bacterial cell killing in normal animals was attributable to the effect of TR-700 (Tedizolid) mediated through granulocytes. (Drusano, G. L., Liu, W., Kulawy, R., & Louie, A. (2011). Impact of granulocytes on the antimicrobial effect of tedizolid in a mouse thigh infection model.Antimicrobial agents and chemotherapy, 55(11), 5300-5305.) (MIC)

d. Human clinical The efficacies of human simulated exposures of tedizolid and linezolid against S. aureus in an immunocompetent mouse thigh model over 3 days were compared. The data support the clinical utility of tedizolid for skin and skin structure infections caused by S. aureus, as well as the bactericidal activity of the oxazolidinones after 3 days of treatment. (Keel, R. A., Tessier, P. R., Crandon, J. L., & Nicolau, D. P. (2012). Comparative efficacies of human simulated exposures of tedizolid and linezolid against Staphylococcus aureus in the murine thigh infection model.Antimicrobial agents and chemotherapy, 56(8), 4403-4407.) trials e. Review Article Tedizolid will provide a useful addition to the antimicrobial armamentarium, particularly in complicated skin and skin structure infections, due to its high oral bioavailability and once-daily dosing. (Kanafani, Z. A., & Corey, G. R. 2012. Tedizolid (TR-701): a new oxazolidinone with enhanced potency. Expert opinion on investigational drugs, 21: 515-522.)

Antibiotic name Ceftaroline (Teflaro) Diseases treated community-acquired m log P-5.719 bacterial pneumonia (CABP) and acute bacterial skin

SMILES IUPAC(6R,7R)-7-[(2Z)-2- MIC values≤2 mg/L for methicillin- ethoxyimino-2-[5- O=C4N3/C(=C(/Sc2nc(c1cc[n+] resistant Staphylococcus aureus (cc1)C)cs2)CS[C@@H]3[C@@ (phosphonoamino)-1,2,4- thiadiazol-3-yl]acetyl]amino]-3- H]4NC(=O)C(=N \OCC)/c5nc(sn [4-(1-methylpyridin-1-ium-4-yl)- 5)NP(=O)(O)O)C([O-])=O 1,3-thiazol-2-yl]sulfanyl]-8-oxo- 5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylate Emp. Formula, Molar mass744.736661 Antibiotic group Cephalosporin Trade namesTeflaro, Zinforo g/mol / C24H25N8O10PS4

2 Dipole Moment (Debye) 5.3 debye Molecular Volume513.703 A3 Surface Area571.48 A

Surface Area (TPSA) 223.248 A2 CAS Number400827-46-5 D/V (dipoe moment/volume)0.0103 Debye/ A3

Rotatable # bonds11 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)16 atoms)4

References and summary MOA Ceftaroline’s mechanism of action is activity against Gram-Positive Pathogens including methicillin resistant, multi- drug resistance, and some gram negative pathogens.It has the ability to bind to penicillin-binding proteins. ( Biek, Donald, et al. "Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity." Journal of antimicrobial chemotherapy 65.suppl 4 (2010): iv9-iv16.)

a. b. Source An advanced-generation cephalosporin antibiotic that is on an unamed subclass of cephalosporins by the CLSI. (Kollef MH (December 2009). "New antimicrobial agents for methicillin-resistant Staphylococcus aureus". Crit Care Resusc (4): 282–6.).

Cell line Test Ceftaroline was tested against strains intracellular forms of S. aureus in comparison with vancomycin, daptomycin and linezolid. (MIC) MIC ≤2 mg/L(Mélard, Aurélie, et al. "Activity of ceftaroline against extracellular (broth) and intracellular (THP-1 monocytes) forms of methicillin-resistant Staphylococcus aureus: comparison with vancomycin, linezolid and daptomycin." Journal of Antimicrobial Chemotherapy 68.3 (2013): 648-658.) c. Human clinical trials Ceftaroline is a novel cephalosporin that has activity against MRSA with phase III clinical trials for complicated skin and skin structure infections with reported non-inferior efficacy against MRSA compared to vancomycin and aztreonamIn 2009, ceftaroline had completed phase III clinical trials for community-acquired pneumonia comparing it against ceftriaxone with non-inferior results and similar adverse reaction profile(P, Eckberg; Friedland HD, et al. "FOCUS 1 and 2: Randomized, Double-blinded, Multicenter Phase 3 Trials of the Efficacy and Safety of Ceftaroline (CPT) vs. Ceftriaxone (CRO) in Community-acquired pneumonia (CAP).". 2009 Interscience Conference on Antimicrobial Agents and Chemotherapy / Infectious Disease Society of America Conference. ) d. . Review Article Farrell, David J., et al. "In vitro activity of ceftaroline against multidrug-resistant Staphylococcus aureus and Streptococcus pneumoniae: a review of published studies and the AWARE Surveillance Program (2008–2010)." Clinical infectious diseases 55.suppl 3 (2012): S206-S214. e.

Antibiotic name Teicoplanin Diseases treated infections caused m log P -1.24 by Gram-positive bacteria, MRSA

SMILES IUPAC Ristomycin A 34-O-[2- MIC values (≥2.0 mg/L) for MRSA. CCCCCCCCCC(=O)NC1C(C(C(OC1OC2=C3C=C4C=C2 (acetylamino)-2-deoxy-.beta.-D- OC5=C(C=C(C=C5)C(C6C(=O)NC(C7=CC(=CC(=C7C8= glucopyranosyl]-22,31-dichloro-7- C(C=CC(=C8)C(C(=O)N6)NC(=O)C4NC(=O)C9C1=CC( demethyl-64-O-demethyl-19-deoxy-56- =CC(=C1)O)OC1=C(C=CC(=C1)C(C(=O)NC(CC1=CC(= O-[2-deoxy-2-[(8-methyl-1- C(O3)C=C1)Cl)C(=O)N9)N)O)O)OC1C(C(C(C(O1)CO) oxononyl)amino]-.beta.-D- O)O)O)O)C(=O)O)OC1C(C(C(C(O1)CO)O)O)NC(=O)C glucopyranosyl]-42-O-.alpha.-D- )Cl)CO)O)O mannopyranosyl-

Emp. Formula, Molar mass Antibiotic group Other Trade names Targocid C88H97Cl2N9O33 Antibiotic- Glycopeptide 1564.3 to 1907.7 g/mol

Dipole Moment (Debye) 17.2 Debye Molecular Volume 1525.45 Å3 Surface Area 1491.41 Å2

2 Surface Area (TPSA) 662.404 Å CAS Number C88H97Cl2N9O33 D/V (dipoe moment/volume) 0.0113 Debye/ Å3

Rotatable # bonds 20 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N) 42 atoms) 25

References and summary a. MOA Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis. (Reynolds, P. E. 1989. Structure, biochemistry and mechanism of action of glycopeptide antibiotics. European Journal of Clinical Microbiology and Infectious Diseases, 8(11), 943- 950.)

b. Source It is a semisynthetic glycopeptide antibiotic with a spectrum of activity similar to vancomycin (Shnayerson, Michael; Plotkin, Mark. 2003. The Killers Within: The Deadly Rise of Drug-Resistant Bacteria. Back Bay Books)

c. Cell line Test Since the of orally administered drugs depend to a great extent on their capability of being transported across the intestinal mucosa., to study the intestinal transport of drugs, an intestinal epithelial cell line (Caco 2) derived from a human colon adenocarcinoma was used. (Ranaldi, G. I. U. L. I. A., Islam, K., & Sambuy, Y. 1992. Epithelial cells in culture as a model for the intestinal transport of antimicrobial agents.Antimicrobial agents and chemotherapy, 36:1374-1381) (MIC) d. Human clinical The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. (Johnson, A. P., Uttley, A. H., Woodford, N., & George, R. C. (1990). Resistance to vancomycin and teicoplanin: an emerging clinical problem.Clinical microbiology reviews, 3:280-291.) trials

e. Review Article Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. (Kalil, A. C., Murthy, M. H., Hermsen, E. D., Neto, F. K., Sun, J., & Rupp, M. E. 2010. Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: A systematic review and meta-analysis*. Critical care medicine, 38:1802-1808.)

Antibiotic name Diseases treated:Skin and skin m log P Telavancin structure infections, pneumonia = 3.091

SMILES IUPAC (1S,2R,18R,19R,22S,25R,28R,40S)-22-(2- MIC values CCCCCCCCCCNCCN[C@]1(C[C@@H](O[C@H]([C@ Amino-2-oxoethyl)-5,15-dichloro-48-{[2-O-(3-{[2- Methicillin-resistant Staphylococcus H]1O)C)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H (decylamino)ethyl]amino}-2,3,6-trideoxy-3-methyl- α-L-lyxo-hexopyranosyl)-β-D-glucopyranosyl]oxy}- aureus (MRSA) ≤1 μg/ml ]2OC3=C4C=C5C=C3OC6=C(C=C(C=C6)[C@H]([C@H 2,18,32,35,37-pentahydroxy-19-[(N-methyl-D- ](C(=O)N[C@H](C(=O)N[C@H]5C(=O)N[C@@H]7C8 leucyl)amino]-20,23,26,42,44-pentaoxo-36- =CC(=C(C=C8)O)C9=C(C(=C(C=C9[C@H](NC(=O)[C@ {[(phosphonomethyl)amino]methyl}-7,13-dioxa- 21,24,27,41,43- H]([C@@H](C1=CC(=C(O4)C=C1)Cl)O)NC7=O)C(=O) pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25 34,39 O)O)CNCP(=O)(O)O)O)CC(=O)N)NC(=O)[C@@H](CC .0 ]pentaconta- (C)C)NC)O)Cl)CO)O)O)C 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene-40-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C80H106Cl2N11O27P , 1755.63 g/mol Lipoglycopeptide Vibativ

Dipole Moment (Debye) Molecular Volume Surface Area 6.91 Debye 1634.39 Å3 1644.10 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 508.916 Å2 372151-71-8 0.004 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 30 available, attached to O, S, N) atoms) 23 40

References and summary a. MOA: Telavancin binds to the D-Ala-D-Ala terminus of the peptidoglycan in cell wall, which in turn inhibits the bacterial cell wall synthesis and causes membrane depolarization. (Higgins, DL; Chang, R; Debabov, DV; Leung, J; Wu, T; Krause, KM; Sandvik, E; Hubbard, JM et al. (2005). "Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus". Antimicrobial Agents and Chemotherapy 49 (3): 1127–1134)

b. Source: Telavancin is a derivative of vancomycin. (Saravolatz, Louis D., Gary E. Stein, and Leonard B. Johnson. "Telavancin: A Novel Lipoglycopeptide." Clinical Infectious Diseases 49.12 (2009): 1908-1914)

c. Cell line Test: The success of telavancin in against three strains of vancomycin- resistant Staphylococcus aureus (VRSA), glycopeptide- intermediate staphylococcal species (GISS), and heteroresistant GISS (hgGISS) was evaluated. Telavancin activity was determined in human serum as well, however the MIC values were found to be lower in tests using telavancin without serum. MIC values for telavancin without serum for VRSAMI, VRSAPA, and VRSANY were 4 mg/L , 2 mg/L , and 2 mg/L respectively. (Leuthner, Kimberly D., Chrissy M. Cheung, and Michael J. Rybak. "Comparative Activity Of The New Lipoglycopeptide Telavancin In The Presence And Absence Of Serum Against 50 Glycopeptide Non-Susceptible Staphylococci And Three Vancomycin-Resistant Staphylococcus Aureus." Journal Of Antimicrobial Chemotherapy 58.2 (n.d.): 338-343.) (MIC) d. Human clinical: Telavancin is used as an interventional therapy for vancomycin-resistant and methicillin-resistant gram-positive cocci for patients with infected abscesses, burns, cellulitis, ulcers, and wound infections. (Theravance, Inc. Phase 2 Trial of TD 6424 (Telavancin) Versus Standard Therapy for Complicated Gram Positive Skin and Skin Structure Infections (Gram Positive cSSSI) (FAST). ClinicalTrails.gov Identifier: NCT00061633. Jan 2010.) trials

e. Review Article: The therapeutic effectiveness of telavancin is evaluated for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) . (Talbot, George H. "Considerations In Undertaking A Clinical Development Program For Hospital-Acquired Bacterial Pneumonia And/Or Ventilator-Associated Bacterial Pneumonia." Clinical Infectious Diseases 51.(2010): S144-S149.)

Antibiotic name Diseases treated Pneumonia, m log p = 3.698 Telithromycin Bronchitis, Sinusitis

SMILES IUPAC MIC values ((1S,2R,5R,7R,8R,9S,11R,13R,14R)-8- O=C2[C@@H]([C@@H](O[C@@H]1O[C@ MIC90 S. pneumonia: 0.125 to 0.5 µg/ml [(2S,3R,4S,6R)- @H](C[C@H](N(C)C)[C@H]1O)C)[C@@]( 4-dimethylamino-3-hydroxy-6-methyl-oxan-2- MIC50/90 Clostridium spp.: ≤ 0.03/0.5 OC)(C)C[C@H](C(=O)[C@H](C)[C@H]3N(C yl]oxy- mg/L 2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl- (=O)O[C@]3(C)[C@H](OC(=O)[C@@H]2C) 15- CC)CCCCn4cc(nc4)c5cccnc5)C)C [4-(4-pyridin-3-ylimidazol-1-yl)butyl]-3,17-dioxa- 15- azabicyclo[12.3.0]heptadecane-4,6,12,16- tetrone Emp. Formula, Molar mass Antibiotic group Trade names

Emp. Formula: C43H65N5O10 First Antibiotic Ketek, Ketek Pak Molar mass: 812.018 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 6.27 Debye 835.88 Å3 789.76 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 171.876 Å2 191114-48-4 0.008 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 12 available, attached to O, S, N) atoms) 1 15

References and summary a. MOA Telithromycin interferes with the synthesis of a bacterial protein. It does this by interacting with the 50S ribosome subunit. (Zhanel, GG., Hisanaga, T., Wierzbowski, A., Hoban, DJ., Telithromycin in the treatment of acute bacterial sinusitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia, Ther., Clin., Risk., Manag., 2(1), 59-75, 2006). 3

b. Source Streptococcus pneumonia (Zhanel, GG., Hisanaga, T., Wierzbowski, A., Hoban, DJ., Telithromycin in the treatment of acute bacterial sinusitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia, Ther., Clin., Risk., Manag., 2(1), 59-75, 2006). 3

c. Cell line Test (MIC) MIC90 S. pneumonia: 0.125 to 0.5 µg/ml (Tessier, PR., Mattoes, HM., Dandekar, PK., Nightingale, CH., Nicolau, DP., Pharmacodynamic Profile of Telithromycin against Macrolide- and Fluroquinolone-Resistant Streptococcus pneumonia in a Neutropenic Mouse Thigh Model, Antimicrob. Agents Chemother., 49(1), 188-194, 2005). 1

MIC50/90 Clostridium spp.: ≤ 0.03/0.5 mg/L (Ackermann, G., Schaumann, R., Pless, B., Claros, C., Rodloff, AC., In vitro activity of telithromycin (HMR 3647) and seven other antimicrobial agents against anaerobic bacteria, J. Antimicrob. Chemother., 46(1), 115-119, 2000). 2

d. Human clinical trials Phase III studies of telithromycin treating community-acquired pneumonia. (Low, DE., Brown, S., Felmingham, D., Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies, Clin., Microbiol., Infect., 10(1), 27-36, 2004). 4 Phase IV studies of telithromycin in Respiratory Tract Infections. Study type: Interventional. Recruitment status: Completed December 2005. e. Review Article 1) Tessier, PR., Mattoes, HM., Dandekar, PK., Nightingale, CH., Nicolau, DP., Pharmacodynamic Profile of Telithromycin against Macrolide- and Fluroquinolone-Resistant Streptococcus pneumonia in a Neutropenic Mouse Thigh Model, Antimicrob. Agents Chemother., 49(1), 188-194, 2005. 2) Ackermann, G., Schaumann, R., Pless, B., Claros, C., Rodloff, AC., In vitro activity of telithromycin (HMR 3647) and seven other antimicrobial agents against anaerobic bacteria, J. Antimicrob. Chemother., 46(1), 115-119, 2000. 3) Zhanel, GG., Hisanaga, T., Wierzbowski, A., Hoban, DJ., Telithromycin in the treatment of acute bacterial sinusitis, acute exacerbations of chronic bronchitis, and community-acquired pneumonia, Ther., Clin., Risk., Manag., 2(1), 59-75, 2006. 4) Low, DE., Brown, S., Felmingham, D., Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies, Clin., Microbiol., Infect., 10(1), 27-36, 2004.

Antibiotic nameTemafloxacin Diseases treatedLower m log P respiratory tract infections 0.367

SMILES IUPAC 1-(2,4-Difluorophenyl)-6- MIC values Temafloxacin was the most

Fc1ccc(c(F)c1)N\3c2cc(c(F)cc2C(=O)C(/C(= fluoro-7-(3-methylpiperazin-1- potent against the M. avium- M.

O)O)=C/3)N4CC(NCC4)C yl)-4-oxoquinoline-3-carboxylic intracellularecomplex, with MICs of 0.2,

acid 0.4, and 0.9 μg/ml.

Emp. Formula, Molar mass Antibiotic groupThird Trade namesOmniflox

C21H18F3N3O3, 417.381 g/mol Generation Quinolones

Dipole Moment (Debye)7.85 Debye Molecular Volume343.728 Å3 Surface Area261.352 Å2

Surface Area (TPSA) 74.569 Å2 CAS Number108319-06-8 D/V (dipoe moment/volume)0.023 Debye/ Å3

Rotatable # bonds3 Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F available, attached to O, S, N)2 atoms)6

References and summary a. MOA Temafloxacin interferes with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram negative bacteria. (Bryskier, A. Fluoroquinolones: mechanisms of action and resistance. Int. J. Antimicrob. Agents 2:151–184, 1993).

b. Source Temafloxacin derives from Nalidixic acid. (Andersson, M.I., MacGowan, A.P. Development of the quinolones. J. Antimicrob. Chemother. 51, p. 1–11, 2001)

c. Cell line Test (MIC) Temafloxacin was the most potent against the M. avium- M. intracellularecomplex, with MICs of 0.2, 0.4, and 0.9 μg/mL. (Gorzynski, E., et al. Comparative antimycobacterial activities of , temafloxacin, enoxacin, pefloxacin, reference fluoroquinolones, and a new macrolide, clarithromycin. Antimicrob. Agents Chemother. 33 (4); p. 591-592, 1989) l

d. Human clinical This study was conducted to determine the toxic potential of Temafloxacin. The four target pints were the kindneys, eyes, central nervous system and weight bearing joints. (Krasula, R., et al. Comparison of organ- specific toxicity of temafloxacin in animals and humans. The American Journal of Medicine. 91 (6); p. s38- s41, 1991) trials

e. Review Article (Ball, P., Fernald, A., Tillotson, G. Therapeutic advances of new fluoroquinolones. Expert Opinion in Investigational Drugs 7, 761–83, 1998).

Antibiotic name Diseases treated m log P Temocillin Treats multi-resistant bacteria =-1.964

SMILES IUPAC MIC values O=C(O)[C@@H]2N3C(=O)[C@@](OC)(NC( (2S,5R,6S)-6-[2-carboxy-2- The MIC value of Temocillin is between =O)C(c1ccsc1)C(=O)O)[C@H]3SC2(C)C (thiophen-3-yl)acetamido]-6- 16- 32 µg/ mL when tested on spectrum methoxy-3,3-dimethyl-7-oxo-4- β-lactamases (ESBLs) and AmpC-type β- thia-1-azabicyclo[3.2.0]heptane- lactamases. 2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names 414.453 g/mol β-lactamase resistant penicillin Temocillinum

Dipole Moment (Debye) Molecular Volume Surface Area 4.87 Debye 362.24 Å3 391.00Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 133.239 Å2 66148-78-5 0.0134 Debye/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 9

References and summary a. MOA The mechanism of action for temocillin is inhibiting the β-lactamase. (Livermore, David M., and Paul M. Tulkens. "Temocillin revived." Journal of antimicrobial chemotherapy 63.2 (2009): 243-245.)

b. Source The source of the drug is it is made synthetically in the same step as penicillin is made. (Newman, David J., and Gordon M. Cragg. "Natural products as sources of new drugs over the 30 years from 1981 to 2010." Journal of natural products 75.3 (2012): 311-335.)

c. Cell line Test (MIC) The MIC value of Temocillin is between 16- 32 µg/ mL when tested on spectrum β-lactamases (ESBLs) and AmpC-type β-lactamases. (Adams-Haduch, Jennifer M., et al. "Activity of temocillin against KPC-producing Klebsiella pneumoniae and Escherichia coli." Antimicrobial agents and chemotherapy 53.6 (2009): 2700-2701.)

d. Human clinical trialsTemocillin Use in Complicated Urinary Tract Infections Due to Extended Spectrum Beta-Lactamases (ESBL)/AmpC Enterobacteriaceae (TEA). The purpose of this test was to study efficacy of temocillin in the treatment of complicated Urinary Tract Infection (UTI) due to confirmed Extended Spectrum Beta-Lactamases. The study was withdrawn prior to Phase 4.

e. Review Article Temocillin in the treatment of Burkholderia cepacia infection in cystic fibrosis (Lekkas, Anastasios, Khin M. Gyi, and Margaret E. Hodson. "Temocillin in the treatment of< i> Burkholderia cepacia infection in cystic fibrosis." Journal of Cystic Fibrosis 5.2 (2006): 121-124.) The article is about a test that was run to research the effectiveness of the drug when given to terminally ill patients.

Antibiotic name Diseases treated m log P Tetracycline Chlamydia = -0.69

SMILESC[C@]1(c2cccc(c2C(=O)C3=C([C@]4([C IUPAC MIC values @@H](C[C@@H]31)[C@@H](C(=C(C4=O)C(=O (4S,6S,12aS)-4-(dimethylamino)- Escherichia coli: 1 μg/ml - >128 μg/ml )N)O)N(C)C)O)O)O)O 1,4,4a,5,5a,6,11,12a-octahydro-

3,6,10,12,12a-pentahydroxy-6- methyl-1,11-dioxonaphthacene- 2-carboxamide

Emp. Formula, Molar mass Antibiotic group Trade names

C22H24N2O8, 444.435 g/mol Tetracyclines Tetracyn, Sumycin

Dipole Moment (Debye) Molecular Volume Surface Area 5.52 Debye 407.46 A3 409.47 A2

Surface Area (TPSA) CAS Number60-54-8 D/V (dipoe moment/volume) 181.684 A2 0.0135 Debye/A3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 2 available, attached to O, S, N) atoms) 10 7

References and summary a. MOATetracycline’s mechanism of action is inhibition of protein synthesis. (Day, L. E. "Tetracycline inhibition of cell-free protein synthesis I. Binding of tetracycline to components of the system." Journal of bacteriology 91.5 (1966): 1917-1923. )

b. SourceTetracycline is derived from the Streptomyces genus of Actinobacteria. (Agersø, Yvonne, and Luca Guardabassi. "Identification of Tet 39, a novel class of tetracycline resistance determinant in Acinetobacter spp. of environmental and clinical origin." Journal of Antimicrobial Chemotherapy 55.4 (2005): 566-569.)

c. Cell line Test (MIC)The MIC value of tetracycline against B. subtilis and S. aureus was 1.50 pg/mL and 2 pg/mL against E. coli. (Bonvehí, Josep Serra, and Francesc Ventura Coll. "The composition, active components and bacteriostatic activity of propolis in dietetics." Journal of the American Oil Chemists’ Society 71.5 (1994): 529-532.)

d. Human clinical trialsTetracycline coupled with streptomycin was tested against human brucellosis. (Ariza, J., et al. "Comparative trial of co-trimoxazole versus tetracycline-streptomycin in treating human brucellosis." Journal of Infectious Diseases152.6 (1985): 1358-1359.)

e. Review Article(Tytgat, G. N. J. "Review article: treatments that impact favourably upon the eradication of Helicobacter pylori and ulcer recurrence." Alimentary pharmacology & therapeutics 8.4 (1994): 359-368.) f. (Penston, J. G. "Review article: Helicobacter pylori eradication–understandable caution but no excuse for inertia." Alimentary pharmacology & therapeutics 8.4 (1994): 369-389.)

Antibiotic name Thiamphenicol Diseases treated m log P -0.358 Gonorrhea

SMILES IUPAC MIC values CS(=O)(=O)C1=CC=C(C=C1)[C@H]([C@@H 2,2-dichloro-N-{(1R,2R)-2- K. pneumonia, 7 µg/mL ](CO)NC(=O)C(Cl)Cl)O hydroxy-1-(hydroxymethyl)-2-[4- (methylsulfonyl)phenyl]ethyl}ace tamide

Emp. Formula, Molar mass Antibiotic group Trade names C12H15Cl2NO5S, 356.223 g/mol Not classified Thiamphenicol

Dipole Moment (Debye) Molecular Volume Surface Area 3.69 Debye 299.30 Å3 332.15 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 103.696 Å3 15318-45-3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA Thiamphenicol inhibits protein synthesis by binding to the 70 S ribosomal subunit preventing peptide bond formation. (Cannon, M., S. Harford and J. Davies. “A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives.” Journal of Antimicrobial Chemotherapy, Vol. 26, No. 3, 307-317, 1990.)

b. Source Chloroamphenicol was originally discovered through sampling micro-organisms found in soil, Thiamphenicol is derived from this. Recently, there have been successful attempts in synthesizing these compounds through stereoselective hydroboration. (Mateus, Cristiano R., & Coelho, Fernando. “An alternative approach to aminodiols from Baylis-Hillman adducts: stereoselective synthesis of chloramphenicol, fluoramphenicol and thiamphenicol.” Journal of the Brazilian Chemical Society, Vol. 16, No. 3a, 386-396, 2005.)

c. Cell line Test (MIC) In vitro susceptibility studies showed thiamphenicol to be effective against a variety of bacterial strains; S. dysenteriase, S. typhi, E. coli, and K. pneumonia, with MIC range of 7 -21 µg/mL. (Syriopoulou, V.P., A. L. Harding, D.A. Goldmann and A.L. Smith. “In Vitro Antibacterial Activity of Fluorinated Analogs of Chloramphenicol and Thiamphenicol.” Antimicrobial Agents and Chemotherapy, Vol. 19, No. 2, 295-297, 1981.)

d. Human clinical trials With gonorrhea developing resistance to other antibiotics, studies were conducted to determine thiamphenicol’s efficacy against N. gonorrhoeae. Results of clinical studies proved thiamphenicol to be effective against strains that had developed resistance to other antibiotic therapies. (De Parra, Cecilia Saad, Henry Leal Cortes, and Jorge Silva Medina.” Clinical Trial of Thiamphenicol Therapy for Uncomplicated Gonorrhea.” Sexually Transmitted Diseases, Vol. 11, No. 4, Oct, 423-425, 1984.)

a. Review Article (Varricchio A., M. Capasso, M. Di Gioacchino, and G. Ciprandi. “Inhaled Thiamphenicol and Acetilcysteine in Children with Acute Bacterial Rhinopharyngitis.” International Journal of Immunopathology and Pharmacology, Vol. 21, No. 3, 583-587, 2008.)

Antibiotic name Diseases treated m log P Ticarcillin Urinary Tract Infections, Skin Infections =0.442

SMILES IUPAC MIC values O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O (2S,5R,6R)-6-{[(2S)-2-carboxy-2- 2-64 µg/ml, )[C@@H](c1ccsc1)C(=O)O)[C@H]3SC2(C) (3-thienyl)acetyl]amino}-3,3- C dimethyl-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names

C15H16N2O6S2, 384.29 g/mol Penicillin Ticar, Timentin

Dipole Moment (Debye) Molecular Volume Surface Area 5.90 Debye 336.69 Å3 363.06 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 124.005 Å2 34787-01-4 0.0175 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 3 8

References and summary a. MOA Ticarcillin's mechanism of action was determined to be preventing cross-linking of peptidoglycan during cell wall synthesis, when the bacteria tries to divide, cell death occurs. (Tenover, F., Mechanisms of Antimocrobial Resistance in Bacteria, Am. J. Med., 19(6) p.3-10, 2006)

b. Source The natural source for the class of Penicillin antibiotics was originally derived from the fungus, Penicillium chrysogenum. (Albang, R., et al, Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum, Nat. Biotech., 26 p.1161-1168, 2008)

c. Cell line Test (MIC) 2-64 µg/ml, Proteus vulgaris, (Fuchs, P., In Vitro Activity of Ticarcillin Plus Clavulanic Acid Against 632 Clinical Isolates, Antimicrob. Agents Chemother., 25(3) p.392-394, 1984)

d. Human clinical trials A combination of ticarcilin and clavulanic acid was administered intravenously to six healthy males, and the concentrations ofthese agents in serum and blisterfluidwere measured. (Bennett, S., et al, Pharmacokinetics and Tissue Penetration of Ticarcillin Combined with Clavulanic Acid, Antimicrob. Agents Chemother., 23(6) p.831-834, 1983)

e. Review Article Ticarcilin-resistant, gram-negative bacili were tested for susceptibility to combinations of ticarcilin and clavulanic acid. (Paisley, J., et al, Combined Activity of Clavulanic Acid and Ticarcillin Against Ticarcillin-Resistant,Gram- Negative Bacilli, 14(2) p.224-227, 1978)

Antibiotic name Diseases treated m log P Tigecycline Complicated skin infections = 0.009

SMILES IUPAC MIC values N-[(5aR,6aS,7S,9Z,10aS)-9- ≤2 μg/ml were obtained when tested CC(C)(C)NCC(=O)Nc1cc(c2C[C@H]3C[C@ [amino(hydroxy)methylidene]- for Enterobacteriaceae H]4[C@H](N(C)C)C(\O)=C(\C(N)=O)C(=O)[ 4,7-bis(dimethylamino)- C@@]4(O)C(/O)=C3/C(=O)c2c1O)N(C)C 1,10a,12-trihydroxy-8,10,11- trioxo-5,5a,6,6a,7,8,9,10,10a,11- decahydrotetracen-2-yl]-2-(tert- butylamino)acetamide Emp. Formula, Molar mass Antibiotic group Trade names C29H39N5O8, 585.65 g/mol Tetracycline Tygacil

Dipole Moment (Debye) Molecular Volume Surface Area 9.39 Debye 565.29 Å3 151.27 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 205.75 Å2 220620-09-7 0.017 D/ Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 7 available, attached to O, S, N) atoms) 8 13

References and summary a. MOA Tigecyclines binds inhibits protein synthesis by binding to the 30S ribosomal subunit of bacteria and thereby blocking entry of Aminoacyl-tRNA into the A site of the ribosome during prokaryotic translation. (Christine, S., et al. Tigecycline: A Novel Broad-Spectrum Antimicrobial. The Annals of Pharmacotherapy. (41)6, p. 965-972, 2007).

b. Source Tigecyclines are semi-synthetic compounds modified from tetracycline. (Lam, K., New aspects of natural products in drug discovery. Trends in microbiology. (15)6, p.279-289,2007).

c. Cell line Test (MIC) MIC values of ≤2 μg/ml were obtained when tested for Enterobacteriaceae . (Milatovic, D., et al. Activities of the tigecycline against 1,924 recent European clinical bacterial isolates. Antimicrobial agents and chemotherapy. (47)1, p. 400-404, 2003).

d. Human clinical trials Tygecycline was used to determine the efficacy and of tigecycline in treating complicated Intra-Abdominal Infections . (Babinchak, T., et al. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infections: analysis of pooled clinical trial data. Clinical infectious diseases . p.354-367, 2005).

e. Review Article A review on the susceptibility of Enterobacteriaceae to tigecycline was carried out with 42 different research studies being evaluated. (Kelesidis, T., et al. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. Journal of antimicrobial chemotherapy. (62)5, p. 895-904, 2008).

Antibiotic name Diseases treated used against m log P tinidazoll protozoan infections = -0.059

SMILES IUPAC MIC values [O -][N+](=O)c1cnc(n1CCS(=O)(=O)CC)C 1-(2-ethylsulfonylethyl)-2- 1.bactericidal concentrations of methyl-5-nitro-imidazole for B. fragilis ranged from 0.25 to 4 μglml3

Emp. Formula, Molar mass Antibiotic group Trade names C8H13N3O4S, 247.273 g/mol Nitroimidazole Tindamax

Dipole Moment (Debye) Molecular Volume Surface Area 1.01 Debye 225.15 Å3 262.32 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 81.832 Å2 19387-91-8 0.0044

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 5 available, attached to O, S, N) atoms) 7 0

References and summary a. MOA Tinidazole inhibit DNA synthesis and degrade existing DNA in exponentially growing cultures of Clostridium bifermentans.(Plant, C.W.,Edward, D.I., The effect of tinidazole, metronidazole and nitrofurazone on nucleic acid synthesis in Clostridium bifermentans, J. Antimicrob. Chemother.,Vol. 2 (2),pg. 203-209,1976

b. Source semi synthetic drug

c. Cell line Test (MIC) The minimum bactericidal concentrations of tinidazole for B. fragilis ranged from 0.25 to 4 μglml.( Jokipii A.M.M., Jokipii L., Bactericidal Activity of Tinidazole, Chemother.,Vol. 23(1),pg.25–31, 1977

d. Human clinical trials 71 patients were enrolled in trial of the use of tinidazole for the prevention of wound infection after elective colonic surgery. 40 patients who were given tinidazole, and eleven wound infections in 31 patients who were given placebo. The difference in wound infection rate between these two groups is significant.( Hunt P.S., Francis J.K., Peck G., Farrell K., Sali, A., Tinidazole in the prevention of wound infection after elective colorectal surgery., The Med. J. Australia,Vol. 1(4),pg.107-109,1979 e. Review Article 1. Scragg J.N., Proctor E.M., Tinidazole treatment of acute amebic dysentery in children., The American J.Trop. Med. and Hyg.,Vol. 26(4),pg.824-825,1977. 2. DENG Li,et al., Study on the Tinidazol and Dexamethasone Stoma Membrane Preparations for Dental Implants,W. china. Med. J.,Vol. 2002(4)pg.532-533. 3. .( Jokipii A.M.M., Jokipii L., Bactericidal Activity of Tinidazole, Chemother.,Vol. 23(1),pg.25–31, 1977

Antibiotic name Diseases treated m log P Tobramycin cystic fibrosis, gram negative infections =5.698

SMILES IUPAC MIC values C1[C@@H]([C@H]([C@@H]([C@H]([C@ (2S,3R,4S,5S,6R)-4-amino-2- 0.25-512 µg/ml, Pseudomonas @H]1N)O[C@@H]2[C@@H]([C@H]([C@ {[(1S,2S,3R,4S,6R)-4,6-diamino- aeruginosa @H]([C@H](O2)CO)O)N)O)O)O[C@@H]3[ 3-{[(2R,3R,5S,6R)-3-amino-6- C@@H](C[C@@H]([C@H](O3)CN)O)N)N (aminomethyl)-5-hydroxyoxan- 2-yl]oxy}-2- hydroxycyclohexyl]oxy}-6- (hydroxymethyl)oxane-3,5-diol Emp. Formula, Molar mass Antibiotic group Trade names C18H37N5O9, 467.52 g/mol Aminoglycoside Tobrex, Tobii

Dipole Moment (Debye) Molecular Volume Surface Area 6.31 Debye 395.43 Å3 418.52 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 268.191 Å2 32986-56-4 0.016 Debye /Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 6 available, attached to O, S, N) atoms) 15 14

References and summary a. MOA The mechanism of action was determined to be binding on to the bacterial 30S and 50S ribosome, which prevents formation of the 70S complex. This inhibits mRNA from being translated into protein and cell death occurs. ( Goffic, L., et al, Mechanism of action of aminoglycoside antibiotics. Binding studies of tobramycin and its 6'-N- acetyl derivative to the bacterial ribosome and its subunits, Eur J Biochem, 102(1), p. 73-81, 1979)

b. Source The natural source of Tobramycin was found to be Streptomyces tenebrarius. ( Kharel, M., et al, Isolation and characterization of the tobramycin biosynthetic gene cluster from Streptomyces tenebrarius, FEMS Microbiology Letters, 230(2), p. 185-190, 2006)

c. Cell line Test (MIC) 0.25-512 µg/ml, Pseudomonas aeruginosa. (Shawar, R., et al, Activities of Tobramycin and Six Other Antibiotics against Pseudomonas aeruginosa Isolates from Patients with Cystic Fibrosis, Antimicrob. Agents Chemother, 43(12), p. 2877-2880, 1999)

d. Human clinical trials A human clinical trial was created to test the efficacy and safety of tobramycin nebuliser solution (TNS) and nebulised colistin in cystic fibrosis patients who were infected with P. aeruginosa. (Hodson, M., et al, A Randomised Clinical Trial of Nebulised Tobramycin or Colistin in Cystic Fibrosis, ERJ, 20(3), p. 658-654, 2002)

e. Review Article Tobramycin proved to be less effective when trying to kill Pseudomonas aeruginosa if the biofilm interior has oxygen limitation and low metabolic activity. (Walters, M., et al, Contributions of Antibiotic Penetration, Oxygen Limitation, and Low Metabolic Activity to Tolerance of Pseudomonas aeruginosa Biofilms to Ciprofloxacin and Tobramycin, Antimicrob. Agents Chemother, 47(1), p. 317-323, 2003)

Antibiotic name Diseases treated m log P Troleandomycin Severe Asthama = 4.491

SMILES IUPAC MIC values O=C(O[C@@H]4[C@@H](N(C)C)C[C (3R,5R,6R,7S,8R,11R,12S,13R,14S,15S 1 µg/ml when used against @H](O[C@H]4O[C@@H]3[C@H]([C@ )-12-[(4-O-acetyl-2,6-dideoxy-3-O- methyl-α-L-arabino- Corynebacterium spp. and Bacillus H](O[C@@H]1O[C@H]([C@H](OC(=O hexopyranosyl)oxy]-14-{[2-O-acetyl- spp. )C)[C@@H](OC)C1)C)[C@H](C(=O)O[ 3,4,6-trideoxy-3-(dimethylamino)-β-D- C@H](C)[C@H](C)[C@H](OC(=O)C)[C xylo-hexopyranosyl]oxy}- @H](C(=O)[C@]2(OC2)C[C@@H]3C)C 5,7,8,11,13,15-hexamethyl-4,10-dioxo- )C)C)C)C 1,9-dioxaspiro[2.13]hexadec-6-yl acetate Emp. Formula, Molar mass Antibiotic group Trade names C41H67NO15, 813.979 g/mol Macrolide Tricetin and Tekmisin

Dipole Moment (Debye) Molecular Volume Surface Area 6.92 Debye 833.69 Å3 839.45 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 132.431 Å2 27512-09-9 0.0083 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 12 available, attached to O, S, N) atoms) 0 16

References and summary a. MOA Macrolides inhibit protein synthesis. They do this by preventing peptidyltransferase and ribosomal translocation. (Gaynor, M., Macrolide Antibiotics: Binding Site, Mechanism of Action, Resistance, Current Topics in Medicinal Chemistry, Vol. 3, No. 9, p. 949-958, 2003)

b. Source Macrolides are produced by bacteria of the Streptomyces spp. (Xue, Y., et al., A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae: Architecture of metabolic diversity, Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 21, p. 12111-12115, 1998)

c. Cell line Test (MIC) Five macrolides were used to test their effects on different types of bacteria. (Le Noc, P., et al., Comparative in vitro bacteriostatic and bactericidal effect of 5 macrolides: roxithromycin, erythromycin, , and spiramycin against 284 hospital bacterial strains, Pathologie-biologie, Vol. 37, No. 5, p. 553-559, 1989)

d. Human clinical trials Patients suffering from severe asthma were treated with Troleandomycin in order to assess its effectiveness. (Evans, D., et al., Troleandomycin as an oral corticosteroid sparing agent in stable asthma, The Cochrane Collaboration, Issue 4, p. 1-3, 2000)

e. Review Article A review on the cardiac effect of Troleandomycin when used for treatment. (Tonini, M., et al., Review article: cardiac adverse effects of gastrointestinal prokinetics, Alimentary Pharmacology & Therapeutics, Vol. 13, Issue 12, p. 1585-1591, 1999)

Antibiotic name Diseases treated m log P Trovafloxacin Gonorrhea = 0.804

SMILESO=C(O)C2=CN(c1nc(c(F)cc1C2=O) IUPAC MIC values N3C[C@H]4[C@H](N)[C@H]4C3)c5ccc(F)c 7-(6-Amino-3- Escherichia coli : 0.25 μg/ml c5F azabicyclo[3.1.0]hex-3-yl)-1- (2,4-difluorophenyl)-6-fluoro- 4-oxo-[1,8] naphthyridine-3- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names Quinolone Trovan C20H15F3N4O3, 413.353 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3 4.23 Debye 327.909 A 390.35 A2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 0.0108 2 101.457A 147059-72-1 Debye/A3 0.0108 Debye/A

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 7 3

References and summary a. MOAThe mechanism of action for trovafloxacin is the inhibition of bacterial topoisomerases. (Bearden, David T., and Larry H. Danziger. "Mechanism of action of and resistance to quinolones." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 21.10P2 (2001): 224S-232S.)

b. SourceTrovafloxacin is a synthetic drug. (Butler, Mark S., and Antony D. Buss. "Natural products—the future scaffolds for novel antibiotics?." Biochemical pharmacology 71.7 (2006): 919-929.)

c. Cell line Test (MIC)The MIC value for trovafloxacin againstPseudomonas aeruginosa was 0.3 μg/ml.( Firsov, Alexander A., et al. "A new approach to in vitro comparisons of antibiotics in dynamic models: equivalent area under the curve/MIC breakpoints and equiefficient doses of trovafloxacin and ciprofloxacin against bacteria of similar susceptibilities." Antimicrobial agents and chemotherapy 42.11 (1998): 2841-2847.)

d. Human clinical trialsTrovafloxacin was tested against drug induced liver injury. (Björnsson, E. "Review article: drug‐induced liver injury in clinical practice."Alimentary pharmacology & therapeutics 32.1 (2010): 3-13.)

e. Review Article(Blondeau, J. M., et al. "Comparative in vitro activity of gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin and trovafloxacin against 4151 Gram-negative and Gram-positive organisms." International journal of antimicrobial agents 14.1 (2000): 45-50. f. (Björnsson, E. "Review article: drug‐induced liver injury in clinical practice."Alimentary pharmacology & therapeutics 32.1 (2010): 3-13.)

Antibiotic name Diseases treated Blood infection, m log P = 0.129 Vancomycin bacterial infection of blood, skin infection

SMILES IUPAC (1S,2R,18R,19R,22S,25R,28R,40S)- 48- MIC values

C[C@H]1[C@H]([C@@](C[C@@H](O1)O[C@@H]2[ {[(2S,3R,4S,5S,6R)- 3- {[(2S,4S,5S,6S)- 4- amino- 5- Staphylococcus aureus: 2 µg/mL C@H]([C@@H]([C@H](O[C@H]2Oc3c4cc5cc3Oc6c hydroxy- 4,6- dimethyloxan- 2- yl]oxy}- 4,5- dihydroxy- 6- (hydroxymethyl)oxan- 2- yl]oxy}- 22- Enterococcus sp.: 16 µg/mL cc(cc6Cl)[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H (carbamoylmethyl)- 5,15- dichloro- 2,18,32,35,37-

]5C(=O)N[C@@H]7c8ccc(c(c8)- pentahydroxy- 19- [(2R)- 4- methyl- 2- c9c(cc(cc9O)O)[C@H](NC(=O)[C@H]([C@@H](c1cc (methylamino)pentanamido]- 20,23,26,42,44- pentaoxo- 7,13- dioxa- 21,24,27,41,43- c(c(c1)Cl)O4)O)NC7=O)C(=O)O)O)CC(=O)N)NC(=O)[ pentaazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25 C@@H](CC(C)C)NC)O)C O)O)O)(C)N)O .034,39]pentaconta- 3,5,8(48),9,11,14,16,29(45),30,32,34,36,38,46,49- pentadecaene- 40- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names Emp. Formula: C66H75Cl2N9O24 Glycopeptides Vancocin, Lyphocin, Vancoled Molar mass: 1449.271 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 3.31 Debye 1301.98 Å3 442.944 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 530.487 Å2 1404-90-6 0.003 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 23 available, attached to O, S, N) atoms) 21 33

References and summary a. MOA Vancomycin inhibits the synthesis of the cell wall. (Hammes, WP., Neuhaus, FC., On the Mechanism of Action of Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari, Antimicrob Agents Chemother, 6(6), 722-728, 1974). 1

b. Source Staphylococcus aureus (Howden, BP., Davies, JK., Johnson, PDR., Stinear, TP., Grayson, ML., Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications., Clin Microbiol Rev., 23(1), 99-139, 2010). 2

c. Cell line Test (MIC) Staphylococcus aureus: 2 µg/mL (Soriano, A., Marco, F., Martínez, JA., Almela, M., Dimova, VP., Alamo, D., Ortega, M., Lopez, J., Mensa, J., Influence of Vancomycin Minimum Inhibitory Concentration on the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia., Clin Infect Dis., 46(2), 193-200, 2008). 3

Enterococcus sp.: 16 µg/mL (Kaplan, AH., Gilligan, PH., Facklam, RR., Recovery of Resistant Enterococci during Vancomycin Prophylaxis., J Clin Microbiol., 26(6), 1216-1218, 1988). 4 d. Human clinical trials Clostridium difficile infection: Phase 3 Trial (Crook, DW., Walker, AS., Kean, Y., Weiss, K., Cornely, OA., Miller, MA., Esposito, R., Louie, TJ., Stoesser, NE., Young, BC., Angus, BJ., Gorbach, SL., Peto, TE., Fidaxomicin versus vancomycin for clostridium difficile infection: meta-analysis of pivotal randomized controlled trials., Clin Infect Dis., 55(2), 93-103, 2012). 5

Nosocomial Neonatal Sepsis: Drug Vancomycin, Phase 3 Clinical Trial. Study type is interventional. e. Review Article 1) Hammes, WP., Neuhaus, FC., On the Mechanism of Action of Vancomycin: Inhibition of Peptidoglycan Synthesis in Gaffkya homari, Antimicrob Agents Chemother, 6(6), 722-728, 1974. 2) Howden, BP., Davies, JK., Johnson, PDR., Stinear, TP., Grayson, ML., Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications., Clin Microbiol Rev., 23(1), 99-139, 2010. 3) Soriano, A., Marco, F., Martínez, JA., Almela, M., Dimova, VP., Alamo, D., Ortega, M., Lopez, J., Mensa, J., Influence of Vancomycin Minimum Inhibitory Concentration on the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia., Clin Infect Dis., 46(2), 193-200, 2008. 4) Kaplan, AH., Gilligan, PH., Facklam, RR., Recovery of Resistant Enterococci during Vancomycin Prophylaxis., J Clin Microbiol., 26(6), 1216-1218, 1988. 5) Crook, DW., Walker, AS., Kean, Y., Weiss, K., Cornely, OA., Miller, MA., Esposito, R., Louie, TJ., Stoesser, NE., Young, BC., Angus, BJ., Gorbach, SL., Peto, TE., Fidaxomicin versus vancomycin for clostridium difficile infection: meta-analysis of pivotal randomized controlled trials., Clin Infect Dis., 55(2), 93-103, 2012.

Antibiotic name Diseases treated m log P Viomycin Tuberculosis = -5.773

SMILES IUPAC MIC values C1[C@@H](NC(=N[C@H]1O)N)[C (S)-3,6-Diamino-N- 10 µg/ml of viomycin inhibits the @H]2C(=O)NC[C@@H](C(=O)N[C ((3S,9S,12S,15S,Z)-((2R,4S)-6- growth of M. smegmatis. amino-4-hydroxy-1,2,3,4- @H](C(=O)N[C@H](C(=O)N/C(=C \ tetrahydropyridin-2-yl)-9,12- NC(=O)N)/C(=O)N2)CO)CO)NC(=O) bis(hydroxymethyl)2,5,8,11,14-

C[C@H](CCCN)N pentaoxo-6-(ureidomethylene)-

1,4,7,10,13-pentaazacyclohexadecan- 15-yl)hexanamide Emp. Formula, Molar mass Antibiotic group Trade names C25H43N13O10 Tuberactinomycin Viocin Sulfate 685.700 g/mol

Dipole Moment (Debye) Molecular Volume Surface Area 1.89 Debye 634.37 Å3 686.21 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 325.965 Å2 32988-50-4 0.00298 (Debye/ Å3)

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 10 available, attached to O, S, N) atoms) 15 13

References and summary a. MOA Viomycin works by inhibiting the biosynthesis of protein in bacteria. (Liou, Y., Tanaka, N., Dual actions of viomycin on the ribosomal functions, Biochem. Biophys. Res. Commun., 71(2), 477-483, 1976.)

b. Source Viomycin was first isolated from the Streptomyces floridae. (Bartz, Q. R., Ehrlich, J., Mold, J. D., Penner, M. A., Smith, R., M., Viomycin, a new tuberculostatic antibiotic, Am. Rev. Tuberc., 63(1), 4-6, 1951.)

c. Cell line Test (MIC) Complete inhibition of M. smegmatis (strain LR 222) was achieved by 10 µg/ml concentration of viomycin. (Johansen, S. K., Maus, C. E., Plikaytis, B. B., Douthwaite, S., Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs, Mol. Cell., 23(2), 173- 182, 2006.)

d. Human clinical trials 171 patients with drug-resistant pulmonary tuberculosis received a combination of four drugs along with viomycin. The usual dosage for viomycin depended on the body weight and was given intramuscularly 5 days a week until 6 months. The cure rate for this study was 49%. (Goble, M., Iseman, M. D., Madsen, L. A., Waite, D., Ackerson, L., Horsburgh, C. R., Treatment of 171 patients with pulmonary ruberculosis resistant to isoniazid and rifampin, New Eng. J. Med. 328(8), 527- 532, 1993.)

e. Review Article [1]. Viomycin, Br. Med. J., 1(5117), 291, 1959. [2]. Today's Drugs: Drugs For Tuberculosis, Br. Med. J., 3(5619), 664-667, 1968.

Antibiotic name Diseases treated m log P 0.38 Besifloxacin Conjunctivitis

SMILES IUPAC MIC values C1CCN(C[C@@H](C1)N)C2=C(C=C3C(=C2 7-[(3R)-3-Aminoazepam-1-yl]-8- Staphylococcus aureus; 0.12 µg/mL Cl)N(C=C(C3=O)C(=O)O)C4CC4)F chloro-1-cyclopropyl-6-fluoro-4- oxo-1,4-dihydroquinoline-3- carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C19H21ClFN3O3, 393.400 g/mol Fluoroquinolone Besivance

Dipole Moment (Debye) Molecular Volume Surface Area 4.48 Debye 364.32 Å3 377.09 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 88.565 141388-76-3 0.0123 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 3 available, attached to O, S, N) atoms) 3 6

References and summary a. MOA Like other fluoroquinolones, besifloxacin targets DNA gyrase and topoisomerase IV in bacterial cells and inhibits DNA replication. Certain features of Besifloxacin’s structure make developing resistance less of a concern. (Comstock, Timothy L., Paul M Karpecki, Timothy W Morris, and Jin-Zhong Zhang. “Besifloxacin: a novel anti- infective for the treatment of bacterial conjunctivitis.” Clinical Ophthalmology, 4, 215–225, 2010.)

b. Source Besifloxacin is a fourth generation fluoroquinolone. Fluoroquinolones are synthetic antibiotics derived from the predecessor of all quinolones, Nalidixic acid. (1. Andersson, Monique I., Alasdair P. MacGowan. “Development of the quinolones”. Journal of Antimicrobial Chemotherapy 51, Suppl. S1, 1–11. 2003)

c. Cell line Test (MIC) Besifloxacin has been found to have a broad spectrum of activity against both aerobic and anaerobic bacteria. This makes it suitable for the treatment of conjunctivitis because of the broad array of bacteria that cause this infection in the conjunctiva. Against Staphylococcus aureus besifloxacin had MIC90 of 0.12 µg/mL. Besifloxacin showed comparable MIC values against over two thousand isolates of 40 bacterial species. (Haas, Wolfgang, Chris M. Pillar, Gary E. Zurenko, Jacqueline C. Lee, Lynne S. Brunner and Timothy W. Morris. “Besifloxacin, a Novel Fluoroquinolone, Has Broad-Spectrum In Vitro Activity against Aerobic and Anaerobic Bacteria.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol. 53, No. 8, 3552–3560, 2009.) d. Human clinical trials A clinical study was carried out to evaluate the pharmacokinetic properties of besifloxacin, and other fluoroquinolones in the conjunctival tissue of healthy volunteers after topical application. Results showed the fluoroquinolones achieved a peak mean concentration 15 minutes after dosing. (Torkildsen, Gail, Joel W Proksch, Aron Shapiro, Stephanie K Lynch, and Timothy L Comstock. “Concentrations of besifloxacin, gatifloxacin, and moxifloxacin in human conjunctiva after topical ocular administration.” Clinical Ophthalmology, 4, 331–341, 2010.) e. Review Article Comstock, Timothy L., Paul M Karpecki, Timothy W Morris, and Jin-Zhong Zhang. “Besifloxacin: a novel anti-infective for the treatment of bacterial conjunctivitis.” Clinical Ophthalmology, 4, 215–225, 2010.)

Antibiotic name Diseases treated m log P -1.019 Cefmenoxime

SMILES IUPAC (6R,7R)-7-{[(2E)-2-(2- MIC values CN1C(=NN=N1)SCC2=C(N3[C@@H]([C@ amino-1,3-thiazol-4-yl)- H. influenzae, 0.39 µg/mL @H](C3=O)NC(=O)/C(=N\OC)/C4=CSC(=N 2-methoxyimino-acetyl]amino}- 4)N)SC2)C(=O)O 3-[(1-methyltetrazol- 5-yl)sulfanylmethyl]-8-oxo-5- thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid

Emp. Formula, Molar mass Antibiotic group Trade names C16H17N9O5S3, 511.562 g/mol Cephalosporin Tacef

Dipole Moment (Debye) Molecular Volume Surface Area 5.87 407.27 Å3 451.03 Å2

Surface Area (TPSA) CAS Number D/V (dipoe moment/volume) 190.829 Å2 65085-01-0 0.014 Debye/Å3

Rotatable # bonds Hydrogen bond Donor (H’s Hydrogen Bond Acceptor (O, S, N, Cl, F 8 available, attached to O, S, N) atoms) 14 4

References and summary a. MOA Cefmenoxime is a β-lactam antibiotic; β-lactams inhibit

b. Source

c. Cell line Test (MIC) Cefmenoxime exhibited a broad spectrum of activity against various bacterial species, the MIC of cefmenoxime of most strains tested by Tsuchiya et. al. was 0.025 µg/mL or less. Against H. influenzae, MIC value was 0.39 µg/mL. (Tsuchiya, K., M. Kondo, M. Kida, M. Nakao, T Iwahi, T. Nishi, Y. Noji, M. Takeuchi, and Y. Nozaki. “Cefmenoxime (SCE-1365), a Novel Broad-Spectrum Cephalosporin: In Vitro and In Vivo Antibacterial Activities.” Antimicrobial Agents and Chemotherapy, Vol. 19, No. 1, 56-65, 1991.) d. Human clinical trials (Granneman GR, LT Sennello, FJ Steinberg, and, RC Sonders. “Intramuscular and intravenous pharmacokinetics of cefmenoxime, a new broad-spectrum cephalosporin, in healthy subjects.” Antimicrobial Agents and Chemotherapy, Vol. 21, No. 1, 141-145, 1982.)

e. Review Article

Graphs and Correlations

Provided below are forty five graphs that provide correlations between the One hundred and eighty seven antibiotic structures the students studied In this project. Many of these parameters have a direct correlation with medicinal activity. We will leave it to the reader to find a hidden gem or two in terms of the correlations between the different parameters.

2500

2000

M M 1500

( g / m o 1000

) l

500

0 0 100 200 300 400 500 600 700 800 TPSA (Å2)

Figure 1. The correlation between the molar mass of 187 antibiotics structures verses the calculated Total Polar Surface area (TPSA, Å2). The best fit line is y = 2.7959x + 0 with a correlation coefficient (R2) of 0.5848. 50

45 D i 40 p o l 35 e

30 M o m 25 e n t 20

( D 15 e b 10 y

) e 5

0 0 20 40 60 80 100 120 140 160 180 200 TPSA (Å2)

Figure 2. The correlation between the dipole moment (DM, Debye) of 187 antibiotics structures verses the calculated Total Polar Surface area (TPSA, Å2). The best fit line is y = 0.0449x with a correlation coefficient (R2) of -.361. 1800

1600

1400

1200

M 1000 V

( Å 800

) 3

600

400

200

0 0 20 40 60 80 100 120 140 160 180 200 TPSA (Å2)

Figure 3. The correlation between the molecular volume (MV, Å3) of 187 antibiotics structures verses the calculated Total Polar Surface area (TPSA, Å2). The best fit line is y = 3.4086x with a correlation coefficient (R2) of -0.855. 30

25

H - B 20 o n d 15 D o n o 10 r s

5

0 0 100 200 300 400 500 600 700 800 TPSA (Å2)

2 Figure 4: The correlation between the H-bond donors vs. the total polar surface area (TPSA),which was in units of Å . The best fit line 2 is y = 0.0379x - 1.0426 with a correlation coefficient (R ) of 0.6697.

50

45 H - 40 B o 35 n d 30

A 25 c c 20 e p 15 t o 10 r s 5

0 0 100 200 300 400 500 600 700 800 TPSA (Å2)

2 Figure 5: The correlation between the H-bond acceptors vs. the total polar surface area (TPSA), which was in units of Å . The best fit 2 line is y = 0.0486x + 2.1225 with a correlation coefficient (R ) of 0.5772.

1800

S 1600 u r 1400 f a 1200 c e 1000

A 800 r e 600

( a Å 400

) 2

200

0 0 100 200 300 400 500 600 700 800

TPSA (Å2)

2 2 Figure 6: The correlation between the surface area in units of Å vs. the total polar surface area (TPSA), which is in units of Å . The best fit line is 2 y = 1.3458x + 178.16 with a correlation coefficient (R ) of 0.2893.

40

35

30

25

20

# of Rotatable Bonds Rotatable of # 15

10

5

0 0 100 200 300 400 500 600 700 800 TPSA (Å2 )

Fig 7: The correlation between total polar surface area (TPSA) of 187 antibiotics structures verses the total number of rotatable bonds. The best fit line is y = 0.0418x + 0.2026 with a correlation coefficient (R2) of 0.64092. 0.25

0.2

) 0.15

3 Debye/ Å

D/V ( 0.1

0.05

0 0 100 200 300 400 500 600 700 800 TPSA (Å2 )

Fig 8: The correlation between total polar surface area (TPSA) of 187 antibiotics structures verses ratios of dipole to molecular volumes (Debye/ Å3). The best fit line is y= -2E-07x + 0.0191 with a correlation coefficient (R2) of 7.2E-07. 10

8

6

4

2

mlog P 0 0 100 200 300 400 500 600 700 800

-2

-4

-6

-8 TPSA (Å2 )

Fig 9: The correlation between total polar surface area (TPSA) of 187 antibiotics structures verses the mlog P values. The best fit line is y = - 0.0053x + 0.682 with a correlation coefficient (R2) of 0.04488. 50

45

40

35

30

25

20 Dipole Dipole Moment (Debye)

15

10

5

0 0 200 400 600 800 1000 1200 1400 1600 1800 2000 MM (g/mol)

Figure 10. The correlation between the molar mass of 187 antibiotics structures verses the calculated Dipole Moment (Debye). The best fit line is y = 0.0049x + 0.0817 with a correlation coefficient (R2) of 0.0817.

1800

1600

1400

1200 ) 3 Å

1000

800 Molecular Volume ( Volume Molecular 600

400

200

0 0 200 400 600 800 1000 1200 1400 1600 1800 2000 MM (g/mol)

Figure 11. The correlation between the molar mass of 187 antibiotics structures verses the calculated Molecular Volume (Å3). The best fit line is y = 0.8084x + 38.674 with a correlation coefficient (R2) of 0.7883.

30

25

20

15

H donors H bond 10

5

0 0 200 400 600 800 1000 1200 1400 1600 1800 2000

-5 MM (g/mol)

Figure 12. The correlation between the molar mass of 183 antibiotics structures verses the calculated number of H bond donors. The best fit line is y = 0.0132x – 1.4781 with a correlation coefficient (R2) of 0.5394.

1800

1600

1400 y = -0.1824x + 404.5 R² = 0.0016 1200

Ǻ²) 1000

800 Surface Area (

600

400

200

0 0 20 40 60 80 100 120 140 160 180 200 Molar Mass (g/mol)

Figure 13. This graph show the linear correlation between the molar mass and the Surface area. The Y-value is y = 0.1824x + 404.5 and the R² = 0.0016. 50

45

40

35

30

25

H H bond Acceptor 20

15

10

5

0 0 20 40 60 80 100 120 140 160 180 200 Molar Mass (g/mol)

Figure 14. This graph show the linear correlation between the molar mass and the Hydrogen bond acceptor. The Y-value is -0.02x + 11.715and the R² = 0.0252. 40

35

30

y = -0.0119x + 7.9708 25 R² = 0.0133

20 Rotatable Bonds Rotatable 15

10

5

0 0 20 40 60 80 100 120 140 160 180 200 Molar Mass (g/mol)

Figure 15. This graph show the linear correlation between the Molar Mass and the Rotatable Bonds. The Y-value is y = -0.0119x + 7.9708 and the R² = 0.0133. 0.25

0.2

) 3 Å 0.15 D/V (Debye/

0.1

0.05

0 0 200 400 600 800 1000 1200 1400 1600 1800 2000 Molar mass (g/mol)

Figure 16. The correlation between the Dipole Moment/Volume of 187 antibiotics structures verses the calculated molar mass. The best fit line is y = -1E-05x +0.0243 with a correlation coefficient (R2) of 0.0189.

10

8

6

4

2

0 0 200 400 600 800 1000 1200 1400 1600 1800 2000 Molar mass (g/mol) mass Molar

-2

-4

-6

-8 mlog P

Figure 17. The correlation between the molar mass (g/mol) of 187 antibiotics structures verses the calculated mlogP. The best fit line is y = 0.0004x + 0.0337 with a correlation coefficient (R2) of 0.0015.

1800

1600

1400

) 1200 3 Å

1000

800

Molecular volume ( volume Molecular 600

400

200

0 0 5 10 15 20 25 30 35 40 45 50 Dipole moment (Debye)

Figure 18. The correlation between the molecular volume of 187 antibiotics structures verses the calculated dipole moment. The best fit line is y = 15.426x + 345.77 with a correlation coefficient (R2) of 0.0846.

30

25

H

20 B o n d 15

D o n 10 o r

5

0 0 5 10 15 20 25 30 35 40 45 50 Dipole Moment(Debye)

Figure 19: The correlation between the Hydrogen bond donor of 187 antibiotics structures verses the calculated Dipole moment (Debye). The best fit line is y = 0.1879X + 3.8533 with a correlation coefficient (R2) of 0.0325.

50

45 H 40 B o 35 n d 30

A 25 c c 20 e p 15 t 10 o r 5

0 0 5 10 15 20 25 30 35 40 45 50 Dipole Moment (Debye)

Figure 20: The correlation between the Hydrogen bond acceptor of 187 antibiotics structures verses the calculated dipole moment (Debye). The best fit line is y = 0.4422x + 7.2255 with a correlation (R2) of 0.0988.

2000

1800

S 1600 u r 1400 f a c 1200 e 1000 A r 800 e

( a 600 Ǻ ^ 400 ) 2

200

0 0 5 10 15 20 25 30 35 40 45 50 Dipole Moment (Debye)

Figure 21: The correlation between the surface area (Ǻ2) of 187 antibiotics structures verses the calculated Dipole Moment (Debye). The best fit line is y = 13.183x + 508.41 with a correlation coefficient (R2) of 0.0005.

40

35

R o 30 t a t 25 a b l 20 e

B 15 o n d 10 s

5

0 0 5 10 15 20 25 30 35 40 45 50 Dipole Moment (Debye)

Figure 22. The correlation between the number of rotatable bonds calculated verses the calculated Dipole Moment (Debye) The best fit line is y = 0.3639x + 4.681with a correlation coefficient (R2) of 0.1051.

0.25

0.2 R o t a a 0.15 b l e

B 0.1 o n d s 0.05

0 0 5 10 15 20 25 30 35 40 45 50 D/V

Figure 23. The correlation between the numbers of rotatable bonds calculated verses the calculated (Dipole Moment)/(Molecular Volume) value. The best fit line is y = 0.0012x + 0.0123 with a correlation coefficient (R2) of 0.0538. 10

8

R 6 o t a 4 t a 2 b l e 0 0 5 10 15 20 25 30 35 40 45 50 B o -2 n d s -4

-6

-8 mlog P

Figure 24. The correlation between the numbers of rotatable bonds calculated verses the calculated mlog P. The best fit line is y = 0.0012x + 0.0123 with a correlation coefficient (R2) of 0.0538.

30

25

20

15 Donor H bonds

10

5

0 0 200 400 600 800 1000 1200 1400 1600 1800 Molecular Volume(Å)

Figure 25. The correlation between the molecular Volume (Å3) of 187 antibiotics structures verses the hydrogen bonds donor. The best fit line is y = 0.0136x – 0.9558 with a correlation coefficient (R2) of 0.4768. 50

45

40

35

30

25

20 Acceptor Bonds Hydrogen 15

10

5

0 0 200 400 600 800 1000 1200 1400 1600 1800 Molecular Volume

Figure 26. The correlation between the molecular Volume (Å3) of 187 antibiotics structures verses the hydrogen bond acceptor . The best fit line is y = 0.0228x – 0.1192 with a correlation coefficient (R2) of 0.7025. 2000

1800

1600

1400

1200

1000 Surface Area 800

600

400

200

0 0 200 400 600 800 1000 1200 1400 1600 1800 Molecular Volume

Figure 27. The correlation between the molecular Volume (Å3) of 187 antibiotics structures verses the calculated Surface area (PSA, Å2). The best fit line is y = 0.3836x + 416.38 with a correlation coefficient (R2) of 0.0012.

40

35

R 30 o t a t 25 a b l 20 e

B 15 o n d 10 s

5

0 0 200 400 600 800 1000 1200 1400 1600 1800 Molecular Volume(Å3)

Figure 28. The correlation between the number of rotatable bonds of 187 antibiotics structures verses the calculated molecular volume (Å3). The best-fit line is y = 0.019x + -1.4399 with a correlation coefficient (R2) of 0.7286.

0.25

0.2

0.15

D / 0.1 V

0.05

0 0 200 400 600 800 1000 1200 1400 1600 1800

-0.05 Molecular Volume (Å3)

Figure 29. The correlation between the dipole moment/molecular volume (Å3) of 187 antibiotics structures verses the calculated molecular volume (Å3). The best fit line is y = -2*10-5 x + 0.026 with a correlation coefficient (R2) of 0.027.

10

8

6

4

m l 2 o g 0 P 0 200 400 600 800 1000 1200 1400 1600 1800

-2

-4

-6

-8 Molecular Volume (Å3)

Figure 30. The correlation between the mlog P of 187 antibiotics structures verses the calculated molecular volume (Å3). The best fit line is y = 0.0004x – 0.3513 with a correlation coefficient (R2) of 0.0017.

50

45

40

35

30

25

H H Bonds Acceptor 20

15

10

5

0 0 5 10 15 20 25 30 H Bonds Donor

Figure 31. The correlation between the hydrogen bonds donors of 187 antibiotics structures verses the hydrogen bonds acceptors. The best fit line is y = 0.9296x + 5.224 with a correlation coefficient (R2) of 0.4535.

1800

1600

1400

1200

1000

800 Surface Area

600

400

200

0 0 5 10 15 20 25 30 H Bonds Donor

Figure 32. The correlation between the hydrogen bonds donors of 187 antibiotics structures verses the surface area. The best fit line is y = 29.759x + 245.25 with a correlation coefficient (R2) of 0.3259.

40

35

30

25

20

Rotatable Bonds Rotatable 15

10

5

0 0 5 10 15 20 25 30 H Bonds Donor

Figure 33. The correlation between the hydrogen bonds donors of 187 antibiotics structures verses the rotatable number of bonds. The best fit line is y = 0.8077x + 2.8411 with a correlation coefficient (R2) of 0.512.

0.25

0.2

0.15

D/V

0.1 y = -0.0004x + 0.0211 R² = 0.0069

0.05

0 0 5 10 15 20 25 30 # H Bonds Donor

Figure 34. A plot of the antibiotics structures dipole moment divided by the number of hydrogen bond donors. The best fit line is y = - 0.0004x + 0.0211 and has a correlation coefficient of R² = 0.0069.

10

8 y = -0.1689x + 0.6896 R² = 0.0995 6

4

2

mlog P 0 0 5 10 15 20 25 30 -2

-4

-6

-8 # H Bond Donor

Figure 35. A plot of the antibiotics structures m logP against the number of hydrogen bond donors. The best fit line is y = -0.1689x + 0.6896 and has a correlation coefficient of R² = 0.0995.

2000

1800

1600

1400

1200

y = 12.565x + 460.45 1000 R² = 0.0009

Surface Area 800

600

400

200

0 0 5 10 15 20 25 30 35 40 45 50 # H Bond Acceptor

Figure 36. A graph of the antibiotics calculated Surface Area verses the number of hydrogen bonds acceptors. The linear best fit line is y = 12.565x + 460.45 with a correlation coefficient of R² = 0.0009.

40

35

R 30 o t a t 25 a b l 20 e

B 15 o n d 10 s

5

0 0 5 10 15 20 25 30 35 40 45 50 H bonds acceptor

Figure 37. The correlation between the rotatable bonds of 187 antibiotics structures versus the hydrogen bonds acceptor. The best fit line is y = 0.693x + 0.0408 with a correlation coefficient (R2) of 0.7183. 0.25

0.2

D / V 0.15

( D e b y e 0.1 / Å

) 3

0.05

0 0 5 10 15 20 25 30 35 40 45 50 H bonds acceptor

Figure 38. The correlation between the dipole moment over molecular volume (Debye/Å3) of 187 antibiotics structures verses the hydrogen bonds acceptor. The best fit line is y = -0.0004x + 0.0227 with a correlation coefficient (R2) of 0.0108. 10

8

6

4

m 2 l o g 0 P 0 5 10 15 20 25 30 35 40 45 50

-2

-4

-6

-8 H bonds acceptor

Figure 39. The correlation between the m logP of 187 antibiotics structures versus the hydrogen bonds acceptor. The best fit line is y = -0.0552x + 0.3881 with a correlation coefficient (R2) of 0.0203. 35

30

25

20

15 Rotatable Bonds Rotatable

10

5

0 0 100 200 300 400 500 600 700 800 900 1000 Surface Area (Ų)

Figure 40. The correlation between the rotatable bonds of 187 antibiotics structures verses the calculated Surface area (Å2). The best fit line is y = 1.4555x + 137.47 with a correlation coefficient (R2) of 0.4133.

0.2

0.15

) ᶾ Å

0.1 D/V (Debye/

0.05

0 0 100 200 300 400 500 600 700 800 900 1000 Surface Area (Ų)

Figure 41. The correlation between the D/V (Debye/Åᶾ) of 187 antibiotics structures verses the calculated Surface area (Å2). The best fit line is y = -1E-07x + 0.0191 with a correlation coefficient (R2) of 0.0003. 10

8

6

4

2

mlog P 0 0 100 200 300 400 500 600 700 800 900 1000

-2

-4

-6

-8 Surface Area (Ų)

Figure 42. The correlation between the mlog P of 187 antibiotics structures verses the calculated Surface area (Å2). The best fit line is y = -1E-05x + 0.1273 with a correlation coefficient (R2) of 0.0001. 0.25

0.2

) 0.15 3 Debye/ Å

D/V ( 0.1

0.05

0 0 5 10 15 20 25 30 35 40 # of Rotatable Bonds

Fig 43: The correlation between the numbers of rotatable bonds of 187 antibiotics structures verses the calculated ratio of dipole to molecular volume (Debye/ Å3). The best fit line is y= -0.0005x + 0.0227 with a correlation coefficient (R2) of 0.0138. 10

8

6

4

2

mlog P 0 0 5 10 15 20 25 30 35 40

-2

-4

-6

-8 # of Rotatable Bonds

Fig 44: The correlation between the numbers of rotatable bonds of 187 antibiotics structures verses the calculated mlog P values. The best fit line is y= -0.036x + 0.09 with a correlation coefficient (R2) of 0.0057. 10

8

6

4

2

mlog P 0 0 0.05 0.1 0.15 0.2 0.25

-2

-4

-6

-8 D/V (Debye/ Å3)

Fig 45: The correlation between the ratios of dipole to molecular volume (Debye/ Å3) of 187 antibiotics structures verses the calculated mlog P values. The best fit line is y = -3.1133x – 0.0741 with a correlation coefficient (R2) of 0.0008. CONCLUSION

There are forty-five graphs that summarize various aspects of the data. Some of the parameters such a logP, TPSA and dipole moment can have a direct correlation with medicinal efficacy. Other parameters that can be directly or indirectly correlated with Lipinski’s rules. We will leave it to the reader to look for correlations that may pertain to their work.

The structures can be downloaded and used by the readers. If any faults are found, please contact Dr. Manning at [email protected] . We will update this list periodically. There have been thousands of antibiotics developed, some of which have limited efficacy against various bacteria. We have tried to focus on the more popular structures. Do not hesitate to contact us with suggestions about adding more structures!

This work was completed by the students of CHEMISTRY 4920 “Antibiotics,” a 2 credit elective offered at Valdosta State University. Many of the students are in a pre-health track (pre-med, pre-dent, pre-pharm, pre-PA, etc.) so this project should assist them in their careers in providing top notch service to our society.

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