Rajiv Gandhi University of Health Sciences s134

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE MISS.CHATURE VANITA VIJAY CANDIDATE AND DEPARTMENT OF PHARMACEUTICAL ADDRESS CHEMISTRY, R.M.E.S’S COLLEGE OF PHARMACY, OLD- JAVERGI ROAD, BALAJI NAGAR, GULBARGA-585102(K.S)

2. NAME OF THE R.M.E.S’S COLLEGE OF PHARMACY, INSTITUTION GULBARGA-585102.

3. COURSE OF STUDY MASTER OF PHARMACY (PHARMACEUTICAL AND SUBJECT CHEMISTRY) 4. DATE OF ADMISSION 30TH JUNE 2009. TO COURSE

5. TITLE OF THE TOPIC:

‘SYNTHESIS AND BIOLOGICAL SCREENING OF SOME NOVEL 1,3,4-THIADIAZOLE DERIVATIVES’

BRIEF RESUME OF THE INTENDED WORK: 6.

6.1 INTRODUCTION :

1,3,4-Thiadiazole derivatives are known to be biologically versatile compounds1. There are the number of five membered heterocyclic ring containing two nitrogen atom and sulphur atom have turned out to be potential chemotherapeutic and pharmacotherapeutic agents2. 1,3,4-thiadiazole derivatives were also reported to posses fungicidal3,4, herbicidal4, pesticidal4, insecticidal4, antihistaminic, and antiamoebic5, cardiotonic5, antihypertensive5, anticonvulsant5, hypnotic, anthelmintic5, analgesic, anti-

1 inflammatory and antioxidant activity6.

6.2 NEED FOR THE STUDY: Recently many drugs have been reported for various diseases developed resistance to existing drugs. Now it is challenging for chemists to find newer molecule with enhanced activity. So, the present study is focused on the development of new potent bioactive, less toxic and easily assessable molecules. The basic objectives of this study are to develop new drug molecules which are helpful to our better social life. Modern therapy is based on scientific observation supported by systemic assessment of the activity of the new molecule, optimization of pharmacological effect, uniform and consistent availability of the drug and the dosage. Thiadiazole is a part of heterocyclic chemistry which contains two N and sulphur and this compound posses wide spectrum of biological and have wide range of therapeutic properties. Various thiadiazole derivatives possess potent pharmacological and biological activity. Therefore it is felt worth while to develop more potent, less toxic and safer drug molecules than existing once. An approach have to be synthesis the same biological molecule containing the thiadiazole nucleus for enhancing better biological activity, that’s why we are choose the new thiadiazole basic ring for synthesis of its derivatives..

6.3 OBJECTIVE: The objectives of present study are to increasing clinical importance of drug resistance of drug molecule which resistant bacterial and fungal pathogen has lent additional urgency to antimicrobial research and development of new antibacterial compounds. Hence, we planned in the present objective of the study will be as below. The work is divided into two phases; 1) Phase I:Synthesis and characterization: i) To synthesis of some Novel 1,3,4- Thiadiazole derivatives. ii) Chemical characterization of the newly synthesized compound by IR, 13C-NMR, 1H-NMR, Mass spectral data.

2) Phase II: Biological screening:

2 Biological screening of some 1.3.4-Thiadiazole derivatives for antimicrobial activity.

6.4 REVIEW OF LITERATURE:

1. Pattan Shashikant R. and coworkers were reported the Synthesis and antimicrobial evaluation of some 1,3,4- Thiadiazole derivatives1.

N N R - Ar S NH

R= - C6H5N2O2 -C7H6NO3 Ar = -C6H4NO2

-C6H6N -C6H6N3O -C6H5O

-C6H5NCl -C4H4N3

2. Somani Rakesh R. and coworkers were reported the synthesis of some 2,5- Disubstituded-1,3,4- Oxadiazole analogues2.

SCH CONRR` O 2

R= -C15H11O2N4SF -C12H14O2N4S

-C15H13O3N4S -C13H14O3N4S

-C15H11O2N4SBr -C14H16O2N4S

3. Namdeo K. P. and coworkers were reported the synthesis of some new 2- (substituted)-5-[(N- Benzotriazolomethyl )-1,3,4-Thiadiazolyl]-4-Thiazolidinones

3 for their Antifungal Activity3.

N NH N N N

NH S 2

4. Kastuyosh Yoneyama and coworkers were reported the Mechanism of Antimicrobial selectivity of 2-amino-1,3,4-Thiadiazole derivatives4.

5. Hatice N. Dogan, Arzu Duran, Seveim Rollas, Goksel Sener, Meral K., UySal and Dumrul Gulen reported Synthesis of New 2,5-Disubstituted- 1,3,4- thiadiazole and preliminary evaluation of Anticonvulsant and Antimicrobial Activities5 N N

NH R S

R= C2H5, Phenethyl , Phenyl, p-Bromophenyl, p-Chlorophenyl, p-Fluorophenyl, p-methoxyphenyle m-trifluoromethylphenyl.

6. Shukurov S. Sh. and coworkers were reported Synthesis of 2-amino-5-aryl-1,3,4- Thiadiazole and their condensed analogs with the use of aromatic nitrines6.

7. Atalay Y., Yakuphanoglu F., Sekerci M., Avci D., Basoglu A. reported Therotical studies of molecular structure and vibrational spectra of 2-amino-5-phenyl-1,3,4- Thiadiazole7.

8. Alireza Foroumadi were reported Synthesis of alkyl alpha-[5-(5-nitro3- thienyl)-1,3,4-thiadiaole-2-yl-thio] acetate8.

4 N N - COOR O + S N S S O R= methyl, ethyl, n-propyl n-butyl, Benzyl,

9. Alireza Foroumad and co-workers were reported the Synthesis of some N-(5- aryl-1,3,4thiadiazole-2-yl) piperazinyl quinolone derivatives9,

N N - Ar Cl S

Ar= C6H4NO2 (p), C6H4NO2(m), C6H4NO2(o), 1-methyl-2-nitro imidazole.

MATERIALS AND METHODS:

7.1 SOURCE OF DATA: 7. The present project is synthesis and chemical characterization of some novel Thiadiazole derivatives and antimicrobial studies. All the basic facilities which are required for synthetic pharmaceutical chemistry are available in our college laboratory. The facilities like apparatus such as glasswares, heating mantle, distillation assembly, melting point apparatus, vaccum pump, chromatography apparatus (chamber); instrument such as IR spectrophotometer and chemicals etc. also available in our college laboratory. The subject will be studied in detail by referring national and international journal of medicinal chemistry, heterocyclic chemistry, for these purpose library and internet facilities are available in our college and also we visit Gulbarga university, Gulbarga; Indian institute of sciences, Bangalore; Indian institute of chemical technology, Hyderabad.

5 7.2 METHOD FOR DATA COLLECTION: The chemical structure of the synthesis compound will be established on the base of physical, chemical and analytical data. Melting point of new compound will be determined in open capillary tube and they are expressed in degree centigrade. The compound synthesis will be characterized by IR, 1H-NMR, 13C-NMR, MASS spectral data. The main objective of this present investigation is to synthesize newer molecules with potent biological activities like antimicrobial activity and antibacterial activity. These newly synthesis molecule will be evaluated for antimicrobial activity by cup-plate diffusion method10. Some selected compounds were screened for biological and pharmacological activities like antihistaminic, anticonvulsant, analgesic, anti-inflammatory, antioxidant activity.

REFERANCES:

6 8. 1. Pattan Shashikant R, Desai N. S. Rabara P. A, Bukitgar A.A, Wakale V.S, Synthesis and antimicrobial evaluation of some 1,3,4- Thiadiaole derivatives, Indian J. Pharm. Educ. Res. 2008; 42(4): 314-318.

2. Somani Rakesh R., Shirodkar Prabhaker Y, Toraskar Mrunmayee P. Kadam Vilasrao J, Synthesis and biological evaluation 2,5-Disubstituded-1,3,4- Oxadiazole analoges, Indian J. Pham. Educ. Res.(2008); 42(1): 53-58.

3. Namdeo K.P, Shigh V.K, Prajapati S. K, Synthesis of some 2-(substituted)-5- [(N-Benzotriazolomethyl)-1,3,4-Thiadiazolyl]-4-Thiazolidinones for their Antifungal Activity, Indian J. Pharm. Educ. Res. (2009);43(3): 266-271.

4. Kastuyosh Yoneyama, Shigeko Sekida, Tomomasa Misato, Mechanism of Antimicrobial selectivity of 2-amino-1,3,4-Thiadiazole derivatives,(1978); 379- 383.

5. Hatice N. Dogan, et.al. Synthesis of New 2,5-Disubstituted- 1,3,4-thiadiazole and preliminary evaluation of Anticonvulsant and Antimicrobial Activities; Bio organic and medicinal chemistry,(2002);10: 2893-2898.

6. Shukurov S. Sh., Kuraniev M. A , Bobogaribar B. M., Sabirav S.S., Synthesis of 2-amino-5-aryl-1,3,4-Thiadiazole and their condensed analogs with the use of aromatic nitrines, Russian Chemical Bulletin,(1995); Volume 44, Number 10: 1955-1956.

7. Atalay Y. , Yakuphanoglu F., Sekerci M., Avci D., Basoglu A., Therotical studies of molecular structure and vibrational spectra of 2-amino-5-phenyl-1,3,4- Thiadiazole, Science Direct, Spectraochimica Acta, (2006); Part A 64: 68-72.

8. Alireza Foroumadi, Zahra Kiani, Fatemeh Soltani, Synthesis and in vitro antibacterial activity of alkyl alpha-[5-(5-nitro3-thienyl)-1-1,3,4-thiadiaole-2-yl-

7 thio]acetate; Science Direct, II Farmaco, (2003) ;58: 1073-1076.

9. Alireza Foroumadi, Fatemeh Soltaani, Mohammad Hasan Moshafi, Rogheeyeh Ashraf-Askari, Synthesis and in vitro antibacterial activity of some N-(5-aryl- 1,3,4thiadiazole-2-yl) piperazinyl quinolone derivatives, II Farmaco, (2003);58: 1023-1028.

10. Indian Pharmacopeia,Vol II (controller of Publication Delhi ) 1996.

11. Arun K.P, Nag V.L, Panda C. S; Studies on the synthesis and bioactivity Of some thiadiazole derivatives. Indian J Chem (1999); 38B:998-1001.

12. Rufen Zhang, Qingfeng Wang, Qianli Li, Chunlin Ma, Synthesis and characterization of triorganotin(IV) complexes of Schiff base derive From 4- amino-5-phenyl-4H-1,2,4-triaole-3-thio and 5-amino-1,3,4-thiadiazole-2-thiol with p-phthalaldehyde, Inorganica Chimica Acta, (2009);362: 2762-2769.

13. Yakuphanoglu F., Yusuf Atalay, Sekerci M., Determination of optical constant of 2-amino-5-phenyl-1,3,4-Thiadiazole by Hartee-Fock and density functional method (B3LYP) Science Direct, Journal of Molecular structure, (2005);779: 72- 76.

14. Gundurao Kolavi, Vinayak Hegde, and Imtiyaz Ahmed Khazi, Syntesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones, Science Direct, Tetrahedron Letters, (2006); 47:2811-2814.

15. Naser Foroughifar, et.al. Synthesis of a new class of azathia crown macrocycles containing two 1,2,4-triazole or two 1,3,4-thiadiazole rings as subunits, Science Direct, Tetrahedron Letters, (2009);50: 836-839.

16. GuoGang Tu, et.al. Novel aminopeptidase N inhibitors derived from 1,3,4- thiadiazole scaffold; Bio organic and medicinal chemistry, (2008) ;16: 6663- 6668.

8 17. Javad Mirzaei, Farideh Siavashi, Saeed Emami, Fatemeh Safari, Mohd. Reza Khoshayands; Synthesis and in vitro anti-Helicobacter Pylori activity of N-[5- (5-nitro-2-heteroaryl) -1,3,4-thiadiazol-yl] thiomorpholines and related compounds; Science Direct, European Journal of medicinal chemistry, (2008); 43:1575-1580.

18. Bellotti A, Coghi E, Baruff A, Pagani G, Borgana B, Inhibition of the hill reaction and phytotoxicities of p-alkyl aniline. Farmaco Ed Sci , (1968);78: 591-593.

19. Kushner S, Cassell Morton J, Williams J.H, Anticonvulsant N-benzilamide.J org Chem. (1951); 16: 1283-1285.

20. Hamm P C, Spezial A J, Effective of variation in acyl moiety on herbicidal activity of n-substituted alpha-chloroacetamides. J Am Pharm. Assoc, (1995); 44:2556-2559.

21. Ferniss B S, Hannaford A J, Smith P W G, Patchel A R, Vogel’s Textbook of Practical organic Chemistry. 5th edition.

22. Jerry March, Reaction Mechanism and Structure. Advance Organic Chemistry, 4th edition.

23. Ahluwalia V K, Parashar R K, Organic Reaction Mechanisms. 2nd edition.

9 10 Signature of Candidate Remark of the guide The above information and literature has been extensively investigated, verified and was found to be correct. The present study will be carried out under my supervision and guidance. Name and Designation of (in block letters)

11.1 Guide MR. KISHORE SINGH M.Pharm. (Ph.D) PROFESSOR, Department of Pharmaceutical chemistry, R.M.E.S’S College of Pharmacy, Gulbarga-585 102

11.2 Signature 11.3 Co-guide (if any) 11.4 Signature

11.5 Head of the Department MR. KISHORE SINGH . M.Pharm.(Ph.D) PROFESSOR & HEAD, Department of Pharmaceutical chemistry, R.M.E.S’S College of Pharmacy, Gulbarga.

11.6 Signature 12.1 Remarks of the The above mentioned information is correct and I Chairman & Principal recommend the same for approval.

12.2 Signature

PROF.HARIPRASSANNA R.C. M.Pharm.(PhD) PRINCIPAL, R.M.E.S’S College of Pharmacy, Gulbarga-585 102