“SYNTHESIS AND ANTIMICROBIAL ACTIVITY

OF SOME NOVEL

THIADIAZOLE DERIVATIVES”

M.PHARM DISSERTATION PROTOCOL

Submitted to

RajivGandhiUniversity of Health Sciences

Bangalore, Karnataka

By

MD. SAQIB

B.Pharm

Under the Guidance of

Mr. KISHORE SINGH. C.

M.Pharm (Ph.D)

Professor

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

R.M.E.S’sCOLLEGE OF PHARMACY,

GULBARGA-585102

2010-2011

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

Curriculum Development Cell

Conformation for Registration of

Subject for Dissertation

Registration No.:

Name of the Candidate:Md. Saqib

Address:R.M.E.S’s College of Pharmacy

Gulbarga, Karnataka.

Name of the Institution:R.M.E.S’s College of Pharmacy

Gulbarga, Karnataka.

Course of Study and Subject:M.Pharm in Pharmaceutical Chemistry

Date of Admission to the Course:30th, June 2009

Title of the Topic:Synthesis and Antimicrobial Activity

of some novel thiadiazole derivatives

Brief resume of the intended work:Enclosed

Signature of the student:

Guide Name:Mr. Kishore Singh. C.

Remarks of the Guide:Recommended

Signature of the Guide:

Co-Guide Name:-

Signature of the Co-Guide:-

HOD Name:Prof. Kishore Singh. C.

Signature of the HOD:

Principal Name:Prof. Hariprasanna R. C.

Mobile No.:9845300610

Principal E-mail ID:

Remarks of the Principal:Recommended for approval

Principal Signature:

Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / Name and Address of the candidate / MD. SAQIB
FATEHPUR TAL RATOY, MAU, UP-221603
2. / Name of the Institution / R.M.E.S’s College of Pharmacy, Gulbarga, Karnataka-585102
3. / Course of study and subject / Master of Pharmacy in Pharmaceutical Chemistry
4. / Date of admission to course / 30/06/2009
5. / Title of the topic / “Synthesis and antimicrobial activity of some novel thiadiazole derivatives”

6. Brief resume of the intended work:

6.1.Introduction

Thiadiazole have received considerable attention during last few decades as they are endowed with various biological activities have wide range of therapeutic properties. Various thiadiazole derivatives posses different pharmacological and biological activities of which the most potent is anti-tubercular activity1, anticonvulsant, sedative-hypnotic and CNS depressant activity2, antitumor3, antimicrobial and anti-inflammatory activity4.

6.2. Need for the study:

Research is never ending process; particularly drug discovery is a continuous process for a lot of reasons like:

a-Some of the drugs are highly effective that are associated with toxic side effects.

b-The pathogenic organisms are known to develop resistance gradually against a particular drug; hence the drugs, which are active today, may become inactive after several years. In order to overcome this problem there is a need to replace old drugs by newer ones.

c-Some drugs have possessed allergic reaction to the some patients.

d-Nature always posses problem to the human races, through new pathogenic bacteria, fungi etc, that cause newer diseases.

Hence man is always in search of more potent and safer drugs than the existing ones. Thiadiazole is a part of heterocyclic chemistry which contains N and S, this compound possesses wide spectrum of biological activity and have wide range of therapeutic properties. Hence the present study is focusing on the development of new potent bioactive, less toxic and easily assembled molecule.

6.3 Review of Literature:

Literature survey reveals that the Thiadiazole has received considerable attention during last two decades as they are endowed with variety of biological activities. These are few literature of Thiadiazole is as under:

  • G. kolavi et. al., have synthesized a series of Imidazo[2,1-b][1,3,4]thiadiazole derivatives and they evaluate their anti-tubercular activity against Mycobacterium tuberculosis1.
R1 / R2 / R3
Cyclohexyl / H / H
Cyclohexyl / Br / H
2-Furyl / H / H
2-Furyl / Br / H
2-Thienyl / H / H
  • D.A Ibrahim has synthesized 3,6-di substituted [1,2,4] triazolo [ 3,4- b] [1,3.4] thiadiazole derivatives and they carried out their anti -tumor activity3

Where,

R= CH3 -CH2Ph -CH2-O-Ph(p-Cl)

  • D Manjunath Ghate et. al., have synthesized 3-alkyl 4-amino 5-mercapto 1,2,4-triazoles (3a-d) treated with different aromatic acid in the presence of phosphorus oxy chloride to yield 3-alkyl-6-aryl-1,2,4-triazolo[3,4b]-1,3,4-thiadiazoles derivatives. All these new heterocycles were screened for their antibacterial, antifungal and anti-inflammatory activity 4
R / Ar
H / p-OCH3C6H4
H / p-Vinyl phenyl
H / p-Chloro phenoxy methyl
CH3 / p-OCH3C6H4
CH3 / p-Vinyl phenyl
  • R.shashikant pattan et. al., were carried out the synthesis of some 1,3,4- Thiadiazole derivatives and they evaluate their antibacterial and antifungal activity 6
R / Ar
  • Ravi S. Lamani et. al., investigated the synthesis of novel methylene bridged benzioxazolyl imidazo[2,1-b] [1,3,4] thiadiazole derivatives from bezioxazolyl-3-acetic acid and thiosemicarbazide and they evaluate their antibacterial and antifungal activity.7

Where,

R= H, Cl, NO2, Br, OMe, 3-Coumarinyl

  • Anelia Ts. Mavrova et. al., synthesized a series of 1,2,4-Triazole and 1,3,4-Thiadiazole derivatives and carried out there cytotoxic activity on immuno-competent cells 9

Where,

R = R1 = -(CH2)4R = R1 = -(CH2)4

R = C6H5 ; R1 = HR = C6H5; R1 = H

  • Sabir Hussain et, al., synthesized a series of 1,2,4-triazole and 1,3,4 thiadiazole derivatives from 5-amino-2-hydroxy benzoic acid and carried out their antibacterial activity against S.aureus (gram positive) and E.coli (gram negative) bacteria and anti fungal activity against A.niger10

III

Ar (I) / Ar (II)

6.4 Objectives:

The increasing clinical importance of drug resistance bacterial and fungal pathogens has lent additional urgency to anti-microbiological research and development of new anti-microbial compound. Hence we planned in the present objectives of the study will be as below:

  1. Development of synthetic method for the synthesis of some 1,3,4 Thiadiazole derivatives.
  2. Chemical characterization of newly synthesized compound by I.R., NMR and Mass spectral data.
  3. Biological screening of 1,3,4 Thiadiazole derivatives for antimicrobial activity.

7. Material and Method:

7.1Source of data:

The present project is synthesis and chemical characterization of some novel thiadiazole derivatives and their antimicrobial studies. All chemicals required for synthesis will be purchased from Aldrich, fluka and S D fine chemicals etc. The subject will be studied in detail by referring national and international journals of medicinal chemistry. Our college has E-library facility to browse all the journals and provide necessary assistance for the student to visit library at IICT, Hyderabad; IISC Bangalore and Gulbarga University, Gulbarga for the literature survey.

7.2 Method of Collection of data:

The chemical structures of the synthesized compounds will be established on the basis of physical, chemical and analytical data. Purification of the synthesized compounds will be done by using re-crystallization techniques. Melting point of the newly synthesized compounds will be analyzed by using open capillary tube method.

The chemical characterization of the newly synthesized compounds will be confirmed by IR, NMR and Mass Spectral Data.

Antimicrobial activity will be carried out by cup plate method or by using micro broth dilution method in our laboratory.

7.3Does the study require any investigation to be conducted on patients or other humans or animals? If so, please describe briefly.

NOT APPLICABLE

7.4Has ethical clearance been obtained from your institution incase of 7.3

NOT APPLICABLE

List of References

  1. Gundurao Kolavi, Vinayak Hegde, Imtiyaz ahmed kazi, and Parmod Gadad. synthesis and evaluation of antitubarcular activity of imidazo[2,1-b] [1,3,4] thiadiazol derivatives.Bioorganic & Medicinal Chemistry 14 (2006):3069-3080
  2. Varsha Jatav,Pradeep Mishra ,Sushil Kashaw ,J.P Stables. Synthesis and CNS depressant activity of some novel 3-[5-subtituted1,3,4-thiadiazole-2-yl] qunazoline-4(3H)-ones. European Journal of Medicinal Chemistry 43 (2008):135-141
  3. D.A.Ibrahim. synthesis and biological evaluation of 3.6-disubstituted[1,2,4]triazolo[3.4-b][1,3,4]thiadiazole derivatives as a novel class of anti-tumor agents. European journals of medicinal chemistry 44(2009):2776-2781
  4. Manjunath Ghate D., Sreenivasa A. Synthesis and Pharmacological activity of 3-Alkyl-6-Aryl-1,2,4-Triazolo[1,3,4]thiadiazole. Indian Journal of Heterocyclic Chemistry Vol.11,Jan-March (2002):225-256
  5. Alireza froumadi, Fatemeh Soltani, Mohammad Hassan Moshafi, Rogheeyeh Ashraf –Askari. Synthesis and in vitro antibacterial activity of some N-(5-aryl-1,3.4-thiadiazole-2-yl) piprazinnyl quinolone derivatives. IL FARMACO 58 (2003): 1023-1028.
  6. Pattan Shashikant R., Desai N.S., Rabara P.A., Bukitgar A.A, Wakale V.S. Synthesis and antimicrobial evaluation of some 1,3,4-thiadiazole.Indian Journal of Pharmaceutical Education & Research Oct-Dec 42(4) (2008):314-318
  7. Ravi S. Lamani, Nitinkumar S.Shetty, Ravindra R.Kamble, Imtiyaz Ahmed M. Khazi. Synthesis and antimicrobial study of novel methylene bridged benzisoxazolyl imidazo[2,1-b][1,3,4] thiadiazole derivatives. European Journal of Medicinal Chemistry 44 (2009):2828-2833
  8. Jag Mohan.Novel Bridgehead Nitrogen heterocyclic system: Facial synthesis, stereochemistry and antimicrobial activity of cis-8-8a-Dihydropyrazolo[3;4;:4.5] thiazolo [2,3-b]-s-triazolo[3,4-b][1,3,4]thiadiazole. Indian Journal of Heterocyclic Chemistry. Oct-Dec (Vol.12) (2002):167-168
  9. Anelia Ts. Mavorva, Diana Wesselinova, Yordan A. Tsenov, Pavletta Denkova. Synthesis, Cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immuno-competent cells. European Journal of Medicinal Chemistry 44(2009): 63-69
  10. Sabir Hussain, Jyoti Sharama and MOHD Amir. Synthesis and anti microbial activities of 1,2,4-triazole and 1,3,4-thiadiazole derivatives of 5-Amino-2-Hydroxybenzoic acid. E-journal of Chemistry, Vol.5, No.4 October (2008):963-968.
  11. GUO Wan-cheng, LIU Xing-hai, LI Yong-hong, WANG Su-hua and LI Zheng-ming. Synthesis and Herbicidal activity of Novel Sulfonylureas containing Thiadiazole moiety. Chem. Res. Chinese. Universities. 24(1)( 2008): 32-35
  12. V. Padmavathi, G.sudhakar Reddy, A.padmaja, P.kondaiah, Ali-shazia. Synthesis, antimicrobial and cytotoxic activity of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. European Journal of Medicinal Chemistry 44 (2009):2106-2112
  13. Michaela Moise, Valeriu Sunel, Lenuta Profire, Marcel Popa, Jacques Desbrieres and Cristian Peptu. Synthesis and biological activity of some new 1,3,4-Thidiazole and 1,2,4-Triazole compounds containing a Phenylalanine Moiety. Molecules 14 (2009):2621-2631
  14. Ferniss B S, Hannaford A. J., Smith PWG, PatchelAR, Vogel’s Text book of Practical Organic Chemistry 5th Edition.
  15. Jerry March, Reaction Mechanism and structure. Advance Organic Chemistry 4th Edition.
  16. Ahluwalia V. K., Parshar R. K., Organic Reaction Mechanism 2nd Edition.
  17. Modern Methods of Organic Synthesis. William Carruthers and Iain Coldham. 4th Edition.

9. / Signature of candidate / MD. SAQIB
10. / 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.
11 / Name & Designation of
11.1 Guide / Mr. Kishore Singh. C.
M.Pharm (Ph.D)
Professor,
Department of Pharmaceutical Chemistry
R.M.E.S.’s College of Pharmacy,
Gulbarga-585102.
11.2 Signature
11.3 Co-Guide (if any) / ------
11.4 Signature / ------
11.5 Head of the Department / Mr. Kishore Singh. C.
M.Pharm (Ph.D)
Professor & Head
Department of Pharmaceutical Chemistry
R.M.E.S.’s College of Pharmacy, Gulbarga.
11.6 Signature
12 / 12.1 Remark of the chairman & principal / The above mentioned information is correct and I recommend the same for approval.
12.2 Signature / Prof. Hari Prasaanna R. C.
M. Pharm (Ph.D.)
Principal
R.M.E.S.’s College of Pharmacy, Gulbarga.