DOCSLIB.ORG

Nitroaromatic Antibiotics As Nitrogen Oxide Sources

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nitroaromatic Antibiotics As Nitrogen Oxide Sources Review biomolecules Nitroaromatic Antibiotics as Nitrogen Oxide Sources Review Allison M. Rice, Yueming Long and S. Bruce King * Nitroaromatic Antibiotics as Nitrogen Oxide Sources Department of Chemistry and Biochemistry, Wake Forest University, Winston-Salem, NC 27101, USA; Allison M. Rice , Yueming [email protected] and S. Bruce (A.M.R.); King [email protected] * (Y.L.) * Correspondence: [email protected]; Tel.: +1-336-702-1954 Department of Chemistry and Biochemistry, Wake Forest University, Winston-Salem, NC 27101, USA; [email protected]: Nitroaromatic (A.M.R.); [email protected] antibiotics (Y.L.) show activity against anaerobic bacteria and parasites, finding * Correspondence: [email protected]; Tel.: +1-336-702-1954 use in the treatment of Heliobacter pylori infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the Abstract: Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding usedevelopment in the treatment of new of Heliobacter treatments pylori forinfections, these conditio tuberculosis,ns, the trichomoniasis, associated toxicity human Africanand lack of clear trypanosomiasis,mechanisms of action Chagas have disease limited and their leishmaniasis. therapeutic Despite development. this activity Nitroaro and a clearmatic need antibiotics for require thereductive development bioactivation of new treatments for activity for theseand this conditions, reductive the associatedmetabolism toxicity can convert and lack the of clear nitro group to mechanismsnitric oxide of (NO) action or have a related limited reactive their therapeutic nitrogen development. species (RNS). Nitroaromatic As nitric oxide antibiotics plays require important roles reductivein the defensive bioactivation immune for activity response and to this bacterial reductive infection metabolism through can convertboth signaling the nitro and group redox-mediated to nitricpathways, oxide (NO) defining or a related controlled reactive NO nitrogen generation species (RNS).pathways As nitric from oxide these plays antibiotics important roleswould in allow the the defensive immune response to bacterial infection through both signaling and redox-mediated design of new therapeutics. This review focuses on the release of nitrogen oxide species from pathways, defining controlled NO generation pathways from these antibiotics would allow the various nitroaromatic antibiotics to portend the increased ability for these compounds to positively design of new therapeutics. This review focuses on the release of nitrogen oxide species from various nitroaromaticimpact infectious antibiotics disease to portend treatment. the increased ability for these compounds to positively impact infectious disease treatment. Keywords: nitroaromatic antibiotics; nitric oxide (NO); nitrite; nitroxyl (HNO); reactive nitrogen Keywords:species (RNS);nitroaromatic infectious antibiotics; diseases; nitric metronidazole oxide (NO); nitrite; nitroxyl (HNO); reactive nitrogen species (RNS); infectious diseases; metronidazole Citation: Rice, A.M.; Long, Y.; King, S.B. Nitroaromatic Antibiotics as Nitrogen Oxide Sources. Biomolecules 1.1. Introduction Introduction 2021, 11, 267. https://doi.org/10.3390/ Citation: Rice, A.M.; Long, Y.; King, Nitroaromatic compounds contain one or more nitro groups directly bonded to an biom11020267 Nitroaromatic compounds contain one or more nitro groups directly bonded to an S.B. Nitroaromatic Antibiotics as aromaticaromatic group group (Figure (Figure1)[1 ].1) [1]. Nitrogen Oxide Sources. Biomolecules Received:2021, 11 25, 267. January https://doi.org/ 2021 Accepted:10.3390/biom11020267 10 February 2021 Published: 12 February 2021 Received: 25 January 2021 Accepted: 10 February 2021 Publisher’s Note: MDPI stays Published: 12 February 2021 neutral with regard to jurisdictional claims in published maps and Publisher’s Note: MDPI stays neutral institutional affiliations. with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. ThisCopyright: article is ©an 2021open by access the authors.article distributedLicensee MDPI,under Basel,the terms Switzerland. and This article is an open access article conditions of the Creative Commons distributed under the terms and Attribution (CC BY) license conditions of the Creative Commons (http://creativecommons.org/licenses Attribution (CC BY) license (https:// /by/4.0/).creativecommons.org/licenses/by/ FigureFigure 1. 1.General General classes classes of biologically of biologically active active nitroaromatic nitroaromatic compounds. compounds. 4.0/). Biomolecules 2021, 11, 267. https://doi.org/10.3390/biom11020267 https://www.mdpi.com/journal/biomolecules Biomolecules 2021, 11, 267. https://doi.org/10.3390/biom11020267 www.mdpi.com/journal/biomolecules Biomolecules 2021, 11, 267 2 of 28 Biomolecules 2021, 11, 267 Numerous nitro heteroaromatic compounds, especially those containing2 ofimidazole 29 and furan or thiophene groups as depicted in Figure 1, demonstrate biological activities allowing for their clinical use as antibiotics and are discussed in this review. NumerousThe chemical nitro and heteroaromatic physical properties compounds, of the especially nitro group those (−NO containing2) including imidazole its electron- andwithdrawing furan or thiophene ability, polarity, groups as size, depicted ability in to Figure form1 ,hydrogen demonstrate bonds biological and redox activities properties allowing[1,2] contribute for their to clinical its key use role as in antibiotics the action and ofare many discussed drugs, in especially this review. antimicrobial agents. NitroaromaticThe chemical compounds and physical find properties use in the of thetrea nitrotment group of a (wide−NO 2variety) including of infectious its electron-withdrawingdiseases for both bacterial ability, infections, polarity, size,including ability tuberculosis to form hydrogen (TB), and bonds parasitic and redox infections propertiessuch as giardiasis, [1,2] contribute trichomoniasis, to its key role human in the action African of many trypanosomiasis drugs, especially (HAT), antimi- Chagas crobialdisease agents. and leishmaniasis, Nitroaromatic compoundswhich are increasingly find use in the becoming treatment global of a wide health variety threats of [3]. infectious diseases for both bacterial infections, including tuberculosis (TB), and parasitic Despite the antibacterial and antiparasitic properties of nitroaromatic antibiotics, drugs infections such as giardiasis, trichomoniasis, human African trypanosomiasis (HAT), Cha- containing nitro groups often demonstrate mutagenicity and unacceptable toxicity gas disease and leishmaniasis, which are increasingly becoming global health threats [3]. Despiteprofiles, the which antibacterial have hindered and antiparasitic further properties development of nitroaromatic of this drug antibiotics, class. drugsThe potent containingbiological nitroactivity groups of often these demonstrate compounds mutagenicity drives andthe unacceptablesearch for toxicitynon-mutagenic profiles, and whichselectively have hinderedtoxic nitroaromatic further development antibiotics of thisthat drug kill the class. infectious The potent agent biological without activity damaging ofhost these cells compounds [1,4]. In addition, drives the repurposing search for non-mutagenic existing nitroaromatic and selectively antibiotics toxic nitroaromatic that have been antibioticsproven safe that represents kill the infectious a less risky agent and without cost-e damagingfficient strategy host cells in [the1,4]. search In addition, of new and repurposingeffective drugs existing to treat nitroaromatic neglected antibiotics tropical diseases that have (NTD) been proven [3]. safe represents a less riskyThe and cost-efficientredox biochemistry strategy in of the the search nitro of newgroup and plays effective a central drugs torole treat in neglected the biological tropicalactivity diseasesof nitroaromatic (NTD) [3]. antibiotics. These compounds require reductive bioactivation for The redox biochemistry of the nitro group plays a central role in the biological activity antimicrobial activity with the reduction being carried out by nitroreductases (NTRs) of of nitroaromatic antibiotics. These compounds require reductive bioactivation for antimi- crobialtype 1 activityor 2 (or with type the reductionI or II, Scheme being carried 1) th outat possess by nitroreductases reducing (NTRs) power of greater type 1 or than 2 the (orreduction type I or II,potential Scheme 1)of that the possess nitroaromatic reducing power compound. greater than Numerous the reduction organism-specific potential ofnitroreductases the nitroaromatic exist compound. as well Numerous as other organism-specific systems nitroreductasesincluding pyruvate/ferredoxin exist as well asoxidoreductase other systems includingand hydrogenases pyruvate/ferredoxin that are capa oxidoreductaseble of catalyzing and hydrogenases nitro group thatreduction are [5– capable10]. of catalyzing nitro group reduction [5–10]. Scheme 1. 1.General General reduction reduction mechanism mechanism of nitroaromatic of nitroaromatic compounds. compounds. These enzymes catalyze nitroaromatic compound (N oxidation state = +3) reduction These enzymes catalyze nitroaromatic compound (N oxidation state = +3) reduction using flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD), and nicoti-
Load more

Recommended publications
  • A Biochemical Rationale for the Discrete Behavior of Nitroxyl and Nitric Oxide in the Cardiovascular System
    A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system Katrina M. Miranda*†‡, Nazareno Paolocci§, Tatsuo Katori§, Douglas D. Thomas*, Eleonora Ford¶, Michael D. Bartbergerʈ, Michael G. Espey*, David A. Kass§, Martin Feelisch**, Jon M. Fukuto¶, and David A. Wink*† *Radiation Biology Branch, Building 10, Room B3-B69, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; §Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; ¶Department of Molecular and Medical Pharmacology, Center for the Health Sciences, University of California, Los Angeles, CA 90095; ʈDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; and **Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130 Edited by Louis J. Ignarro, University of California School of Medicine, Los Angeles, CA, and approved May 20, 2003 (received for review February 20, 2003) The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often cellular thiol functions (14, 15). Conversely, NO reacts only indi- been assumed to undergo casual redox reactions in biological sys- rectly with thiols after RNOS formation (17). tems. However, several recent studies have demonstrated distinct Contrasting effects are also apparent in vivo or ex vivo,for pharmacological effects for donors of these two species. Here, infu- example in models of ischemia reperfusion injury. Exposure to NO sion of the HNO donor Angeli’s salt into normal dogs resulted in donors at the onset of reperfusion provides protection against elevated plasma levels of calcitonin gene-related peptide, whereas reperfusion injury in the heart and other organs (18–20).
    [Show full text]
  • Increased Urinary Nitrate Excretion in Rats with Adjuvant Arthritis
    Annals of the Rheumatic Diseases 1994; 53: 547-549 547 Ann Rheum Dis: first published as 10.1136/ard.53.8.547 on 1 August 1994. Downloaded from Increased urinary nitrate excretion in rats with adjuvant arthritis Dirk 0 Stichtenoth, Frank-M Gutzki, Dimitrios Tsikas, Norma Selve, Stefanie M Bode-Boger, Rainer H Boger, Jurgen C Frolich Abstract well established model ofpolyarthritis. For this Objectives-In rats with adjuvant arthritis we applied a recently developed, highly spec measurements were taken of the urinary ific and sensitive gas chromatographic method excretion ofnitrate, reflecting endogenous for determination of nitrite and nitrate in nitric oxide (NO) formation, and cyclic serum, urine, synovia and cell supernatants. guanosine monophosphate (cGMP). NO itself is difficult to measure directly, Methods-Urinary nitrate was deter- because of its very short half life in biological mined by gas chromatography, cGMP by fluids. NO is readily oxidised to nitrite and radioimmunoassay. nitrate,7 which are excreted rapidly into urine. Results-A significant (p < 0.001), more It has been shown, that the major source of than three fold increase of urinary nitrate urinary nitrate, in the absence of excess nitrate excretion was found in rats 20 days after intake in food, is endogenously synthesised induction of adjuvant arthritis compared NO.8 Therefore the NO synthase activity can with non-arthritic rats. There was no be assessed reliably by measuring urinary significant difference in urinary cGMP nitrate excretion, as reported by Suzuki et al9 excretion between arthritic rats and and our group (Bode-Boger et al). control animals. Conclusion-The data suggest that the dramatic increase of urinary nitrate ex- Materials and methods cretion is due to increase of NO synthesis ANIMALS AND ARTHRITIS INDUCTION by the inducible form ofNO synthase.
    [Show full text]
  • Fexinidazole – New Orphan Drug Approval
    Fexinidazole – New orphan drug approval • On July 19, 2021, Sanofi announced the FDA approval of fexinidazole, for the treatment of both the first-stage (hemolymphatic) and second-stage (meningoencephalitic) human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense (T. brucei gambiense) in patients 6 years of age and older and weighing at least 20 kg. — Due to the decreased efficacy observed in patients with severe second stage HAT (cerebrospinal fluid white blood cell count > 100 cells/µL) due to T. brucei gambiense disease, fexinidazole should only be used in these patients if there are no other available treatment options. • Sleeping sickness is a parasitic disease transmitted by the bite of an infected tse-tse fly. It affects mostly populations living in remote rural areas of sub-Saharan Africa. Left untreated, sleeping sickness is almost always fatal. — According to the CDC, less than 100 cases of sleeping sickness have been reported annually to the World Health Organization. Infection of international travelers is rare, but it occasionally occurs and most cases of sleeping sickness imported into the U.S. have been in travelers who were on safari in East Africa. • The efficacy of fexinidazole was established in a randomized, comparative open-label trial in 394 adult patients with late second-stage HAT due to T. brucei gambiense. Patients were randomized to a 10-day treatment regimen of either fexinidazole or nifurtimox-eflornithine combination therapy (NECT). The outcome at 18 months was considered a success if patients were classified as a cure or probable cure. — Success at 18 months was achieved in 91.2% of patients treated with fexinidazole vs.
    [Show full text]
  • The National Drugs List
    ^ ^ ^ ^ ^[ ^ The National Drugs List Of Syrian Arab Republic Sexth Edition 2006 ! " # "$ % &'() " # * +$, -. / & 0 /+12 3 4" 5 "$ . "$ 67"5,) 0 " /! !2 4? @ % 88 9 3: " # "$ ;+<=2 – G# H H2 I) – 6( – 65 : A B C "5 : , D )* . J!* HK"3 H"$ T ) 4 B K<) +$ LMA N O 3 4P<B &Q / RS ) H< C4VH /430 / 1988 V W* < C A GQ ") 4V / 1000 / C4VH /820 / 2001 V XX K<# C ,V /500 / 1992 V "!X V /946 / 2004 V Z < C V /914 / 2003 V ) < ] +$, [2 / ,) @# @ S%Q2 J"= [ &<\ @ +$ LMA 1 O \ . S X '( ^ & M_ `AB @ &' 3 4" + @ V= 4 )\ " : N " # "$ 6 ) G" 3Q + a C G /<"B d3: C K7 e , fM 4 Q b"$ " < $\ c"7: 5) G . HHH3Q J # Hg ' V"h 6< G* H5 !" # $%" & $' ,* ( )* + 2 ا اوا ادو +% 5 j 2 i1 6 B J' 6<X " 6"[ i2 "$ "< * i3 10 6 i4 11 6! ^ i5 13 6<X "!# * i6 15 7 G!, 6 - k 24"$d dl ?K V *4V h 63[46 ' i8 19 Adl 20 "( 2 i9 20 G Q) 6 i10 20 a 6 m[, 6 i11 21 ?K V $n i12 21 "% * i13 23 b+ 6 i14 23 oe C * i15 24 !, 2 6\ i16 25 C V pq * i17 26 ( S 6) 1, ++ &"r i19 3 +% 27 G 6 ""% i19 28 ^ Ks 2 i20 31 % Ks 2 i21 32 s * i22 35 " " * i23 37 "$ * i24 38 6" i25 39 V t h Gu* v!* 2 i26 39 ( 2 i27 40 B w< Ks 2 i28 40 d C &"r i29 42 "' 6 i30 42 " * i31 42 ":< * i32 5 ./ 0" -33 4 : ANAESTHETICS $ 1 2 -1 :GENERAL ANAESTHETICS AND OXYGEN 4 $1 2 2- ATRACURIUM BESYLATE DROPERIDOL ETHER FENTANYL HALOTHANE ISOFLURANE KETAMINE HCL NITROUS OXIDE OXYGEN PROPOFOL REMIFENTANIL SEVOFLURANE SUFENTANIL THIOPENTAL :LOCAL ANAESTHETICS !67$1 2 -5 AMYLEINE HCL=AMYLOCAINE ARTICAINE BENZOCAINE BUPIVACAINE CINCHOCAINE LIDOCAINE MEPIVACAINE OXETHAZAINE PRAMOXINE PRILOCAINE PREOPERATIVE MEDICATION & SEDATION FOR 9*: ;< " 2 -8 : : SHORT -TERM PROCEDURES ATROPINE DIAZEPAM INJ.
    [Show full text]
  • Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
    International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1.
    [Show full text]
  • (12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak Et Al
    US008343962B2 (12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak et al. (45) Date of Patent: *Jan. 1, 2013 (54) TOPICAL FORMULATION (58) Field of Classi?cation Search ............. .. 514/226.5, 514/334, 420, 557, 567 (75) Inventors: Edward T. Kisak, San Diego, CA (US); See application ?le fOr Complete Search history. John M. NeWsam, La Jolla, CA (US); _ Dominic King-Smith, San Diego, CA (56) References C‘ted (US); Pankaj Karande, Troy, NY (US); Samir Mitragotri, Goleta, CA (US) US' PATENT DOCUMENTS 5,602,183 A 2/1997 Martin et al. (73) Assignee: NuvoResearchOntano (CA) Inc., Mississagua, 6,328,979 2B1 12/2001 Yamashita et a1. 7,001,592 B1 2/2006 Traynor et a1. ( * ) Notice: Subject to any disclaimer, the term of this 7,795,309 B2 9/2010 Kisak eta1~ patent is extended or adjusted under 35 2002/0064524 A1 5/2002 Cevc U.S.C. 154(b) by 212 days. FOREIGN PATENT DOCUMENTS This patent is subject to a terminal dis- W0 WO 2005/009510 2/2005 claimer- OTHER PUBLICATIONS (21) APPI' NO‘, 12/848,792 International Search Report issued on Aug. 8, 2008 in application No. PCT/lB2007/0l983 (corresponding to US 7,795,309). _ Notice ofAlloWance issued on Apr. 29, 2010 by the Examiner in US. (22) Med Aug- 2’ 2010 Appl. No. 12/281,561 (US 7,795,309). _ _ _ Of?ce Action issued on Dec. 30, 2009 by the Examiner in US. Appl. (65) Prior Publication Data No, 12/281,561 (Us 7,795,309), Us 2011/0028460 A1 Feb‘ 3’ 2011 Primary Examiner * Raymond Henley, 111 Related U 5 Application Data (74) Attorney, Agent, or Firm * Foley & Lardner LLP (63) Continuation-in-part of application No.
    [Show full text]
  • Biopharmaceutical Optimization in Neglected Diseases for Paediatric Patients by Applying the Provisional Paediatric Biopharmaceu
    Gonzalez-Alvarez Isabel (Orcid ID: 0000-0002-1685-142X) i. Title (including PI’s name) “Biopharmaceutical Optimization in neglected diseases for paediatric patients by applying the provisional paediatric Biopharmaceutical Classification System” Principal investigator: Gordon L. Amidon Author for correspondence: [email protected] ii. Short running title of less than 40 characters Paediatric Biopharmaceutical Optimization in Neglected Diseases iii. The full names of all authors Jose Manuel del Moral Sanchez (delMoral-Sanchez JM) Isabel Gonzalez Alvarez (Gonzalez-Alvarez I) Aaron Cerda Revert (Cerda-Revert A) Marta Gonzalez Alvarez (Gonzalez-Alvarez M) Andres Navarro Ruiz (Navarro A) Gordon L. Amidon (Amidon GL) Marival Bermejo Sanz (Bermejo M) This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.13650 This article is protected by copyright. All rights reserved. iv. The authors’ institutional affiliations (ie where the work was carried out, with a footnote for an author’s present address if different from where the work was carried out) Jose Manuel del Moral Sanchez (delMoral-Sanchez JM) 1Institute of Molecular and Cellular Biology of Miguel Hernandez University. Avda de la Universidad s/n, 03202 Elche (Alicante) Spain 2Department of Pharmacokinetics and Pharmaceutical Technology,
    [Show full text]
  • Insights of Antiparasitic Activity of Sodium Diethyldithiocarbamate Against Different Strains of Trypanosoma Cruzi
    www.nature.com/scientificreports OPEN Insights of antiparasitic activity of sodium diethyldithiocarbamate against diferent strains of Trypanosoma cruzi Johny Wysllas de Freitas Oliveira1,2, Tafarel Melo Torres3, Cláudia Jassica Gonçalves Moreno1,2,4, Bruno Amorim‑Carmo2, Igor Zumba Damasceno5, Ana Katarina Menezes Cruz Soares6, Jeferson da Silva Barbosa7, Hugo Alexandre Oliveira Rocha2,6 & Marcelo Sousa Silva1,2,4,8* Chagas disease is caused by Trypanosoma cruzi and afects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against diferent strains and forms of T. cruzi and their mechanism. The diferent strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Diferent response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against diferent genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.
    [Show full text]
  • A Review of Enrofloxacin for Veterinary Use Tessa Trouchon, Sebastien Lefebvre
    A Review of Enrofloxacin for Veterinary Use Tessa Trouchon, Sebastien Lefebvre To cite this version: Tessa Trouchon, Sebastien Lefebvre. A Review of Enrofloxacin for Veterinary Use. Open Journal of Veterinary Medicine, 2016, 6 (2), pp.40-58. 10.4236/ojvm.2016.62006. hal-01503397 HAL Id: hal-01503397 https://hal.archives-ouvertes.fr/hal-01503397 Submitted on 7 Apr 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NoDerivatives| 4.0 International License Open Journal of Veterinary Medicine, 2016, 6, 40-58 Published Online February 2016 in SciRes. http://www.scirp.org/journal/ojvm http://dx.doi.org/10.4236/ojvm.2016.62006 A Review of Enrofloxacin for Veterinary Use Tessa Trouchon, Sébastien Lefebvre USC 1233 INRA-Vetagro Sup, Veterinary School of Lyon, Marcy l’Etoile, France Received 12 January 2016; accepted 21 February 2016; published 26 February 2016 Copyright © 2016 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Abstract This review outlines the current knowledge on the use of enrofloxacin in veterinary medicine from biochemical mechanisms to the use in the field conditions and even resistance and ecotoxic- ity.
    [Show full text]
  • Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis
    ORIGINAL RESEARCH published: 13 April 2021 doi: 10.3389/fphar.2021.636265 Efficacy of Spironolactone Treatment in Murine Models of Cutaneous and Visceral Leishmaniasis Valter Viana Andrade-Neto 1, Juliana da Silva Pacheco 1,2, Job Domingos Inácio 1, Elmo Eduardo Almeida-Amaral 1, Eduardo Caio Torres-Santos 1* and Edezio Ferreira Cunha-Junior 1,3* 1Laboratorio de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil, 2Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom, 3Laboratório de Imunoparasitologia, Unidade Integrada de Pesquisa em Produtos Bioativos e Biociencias,ˆ Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, Brazil Translational studies involving the reuse and association of drugs are approaches that can result in higher success rates in the discovery and development of drugs for serious public health problems, including leishmaniasis. If we consider the number of pathogenic species in relation to therapeutic options, this arsenal is still small, and Edited by: each drug possesses a disadvantage in terms of toxicity, efficacy, price, or treatment Paula Gomes, regimen. In the search for new drugs, we performed a drug screening of L. University of Porto, Portugal amazonensis promastigotes and intracellular amastigotes of fifty available drugs Reviewed by: Manoj Kumar Singh, belonging to several classes according to their pharmacophoric group. Adamas University, India Spironolactone, a potassium-sparing diuretic, proved to be the most promising Adnan Ahmed Bekhit, Alexandria University, Egypt drug candidate. After demonstrating the in vitro antileishmanial activity, we fi *Correspondence: evaluated the ef cacy on a murine experimental model with L.
    [Show full text]
  • Template for Electronic Submission to ACS Journals
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Kingston University Research Repository Selective Methylmagnesium Chloride Mediated Acetylations of Isosorbide: A Route to Powerful Nitric Oxide Donor Furoxans Patrick Kielty,† Dennis A. Smith,† Peter Cannon,‡ Michael P. Carty,§ Michael Kennedy,† Patrick McArdle,† Richard J. Singer,‖ and Fawaz Aldabbagh*,†, ⊥ † School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland ‡ Avara Pharmaceutical Services, Shannon Industrial Estate, Shannon, Co. Clare, V14 FX09, Ireland § Biochemistry, School of Natural Sciences, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland ‖ Department of Chemical and Pharmaceutical Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, KT1 2EE, UK Present address: Department of Pharmacy, School of Life Sciences, Pharmacy & Chemistry, Kingston University, Penrhyn Road, Kingston upon Thames, KT1 2EE, UK ⊥ ABSTRACT: Isosorbide was functionalized with furoxan for the first time to give adducts that release nitric oxide up to 7.5 times faster than the commercial vasodilator, isosorbide-5-mononitrate (Is5N). The synthesis was facilitated by MeMgCl-mediated selective acetylation of isosorbide or selective deacetylation of isosorbide-2,5- diacetate, which was rationalised in terms of a more stable 5- alkoxide magnesium salt using DFT. Isosorbide-furoxans are safer to handle than Is5N due to greater thermal stability. Nitric oxide (NO) is a reactive free radical with a vast array of Scheme 1. (A) Is5N and furoxan drugs (B) Protection- physiological functions,1 in cancer,2 anti-microbial deprotection of isosorbide 1 allowing selective func- processes,3 wound healing,4 and most significantly, tionalization with furoxan vasodilation.5 Clinically, nitrate ester drugs are used to effect vasodilation.
    [Show full text]
  • ) Synthesis of Quinoline and Derivatives1)
    Faculty of Science Damietta University Chemistry Department An Essay on : Evaluation of the Synthesis, Reactions and Biological Activities of Quinolines _______________________________________________________________________ ____________________________________________________________ Presented BY MOHAMED ELNEKETY b.s.C student (special 2016 chemistry) Acknowledgment First my thank and gratitude to Allah I am greatly indebted to Prof.Dr : FAWZIA EL-ABLACK Professor of Organic Chemistry Chemistry Department Faculty of Science Damietta University To his supervision on my research. He taught me How to design a research plan and how to write it. I appreciate your help, guiding and encouragement. Again many thanks for what you have done for me. Fourth year Chemistry Department 2015 - 2016 Contents : Page Introduction..……………………………………..…………………….…..3 (1) Synthesis of Quinolines………………….………….…….…....5 1.1 Skraup reaction…………………………………………………..5 1.2 Combes quinoline synthesis…………………………….…….…6 1.3 Doebner reaction..………………………………..…….………..6 1.4 Doebner–Miller reaction …………………………….………….7 1.5 Knorr quinoline synthesis…………………………….…………7 1.6 Friedlaender Synthesis……………………………….………….8 1.7 Pfitzinger Synthesis………………………………….…………..8 1.8 Green preparation of quinolone……………………….……….9 1.9 Quinolines by Forming the N–C-2 Bond……………….……...11 1.10 From Aldehyde and Aniline……………………………………11 1.11 By condensation reaction of ortho-acylanilines and Alkenyl iodides…………………………………………….……12 1.12 By dehydrogenation of tetrahydroquinolines………….……..12 1.13 By cyclization of 2-ethynylanilines
    [Show full text]