SYNTHESIS AND BIOLOGICAL EVALUATION OF NEWER ANALOGUES OF 2,5-DISUBSTITUTED-1,3,4-OXADIAZOLE AS ANTIMICROBIAL, ANTIOXIDANT AND ANTI CONVULSANT AGENTS.

SYNOPSIS FOR REGISTRATION

OF

M.PHARM DISSERTATION

Submitted to

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

KARNATAKA

By:-

ARUN DUREJA

IST M.PHARM

Department Of Pharmaceutical Chemistry

DAYANANDA SAGAR COLLEGE OF PHARMACY

2009

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate
and Address /
Arun Dureja
S/O Sh. Hari Krishan Dureja
VPO- Urlana Kalan, Distt.- Panipat (HARYANA)-132103
.
2. / Name of the Institution / Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 560 078.
3. / Course of Study and
Subject / M. Pharm in Pharmaceutical Chemistry
4. / Date of Admission / 23rd JUNE-2009
5. Title of The topic :

“Synthesis and biological evaluation of newer analogues of 2,5-disubstituted-1,3,4-oxadiazole as Antimicrobial, Antioxidant and Anticonvulsant agents”


R= Substituted aldehydes
6.0
/ Brief resume of the intended work:
6.1 – Need for the study:
The synthesis, structure and biological activity of oxadiazole derivatives have long been the focus of research interest in the field of medicine. A number of derivatives of substituted oxadiazole have been reported to possess several biological activities such as Antimicrobial1,2,3, Anti Tubercular4,5, Antioxidant6, Anti Convulsant7,8 and Anti inflammatory9,10,11.
Although several Antibacterial agents were synthesized in 20th century, most of the bacteria have become resistant to these agents and there is a need to synthesize newer compounds. Tuberculosis is the leading killer of the youth women and aids patients all over the world. Although many Anti tubercular agents have been synthesized, the problem with the use of present drugs as a single agent has developed drug resistance. The development of Multi Drug Resistance of Mycobacterium tuberculosis together with the spread of disseminated infections produced by Mycobacteria other than tuberculosis particularly by Mycobacterium avium in immunocompromised patients prompts the search for new Anti Mycobacterial drugs. It is observed from literature that certain five membered heterocyclic compounds such as oxadiazole as basic ring possess significant anti tubercular activity with lesser side effects.
Overproduction of free radicals and other reactive oxygen species can cause oxidative damage to biomolecules (DNA, lipids etc). From the literature it is learnt that oxadiazole contains free radical scavenging activity. Hence an attempt will be made to carry out Antioxidant activity for the prepared compounds.
Despite introduction of various Anticonvulsant agents, chronic patients face specific problems of neurotoxicity, depression and CNS related problems which proposed us to synthesize newer agents such as substituted oxadiazoles with lesser complications.
7.0 / SCHEME:-
Salicyldehyde is treated with Diethyl Malonate to yield coumarin-3-ethyl carboxylate. This on treatment with hydrazine hydrate gives hydrazone. The hydrazone so obtained, will be treated with various substituted Aldehydes to get corresponding arylidines, which on refluxation in presence of acetic anhydride yields substituted oxadiazole derivatives.
6.2 – Review of the literature:
1. Zuhair Muhi-eldeen et. al1 have reported Antimicrobial activity of some new Oxadiazole derivatives. The most promising compound as Antibacterial was identified and named as 5-(pyridyl)-1,3,4-oxadiazole-2-benzylthiocarbamates. They
observed that some oxadiazoles with different substituents at different location on
the heterocyclic ring resulted in fungicidal and antibacterial agents of various
potencies.
2. Iqbal R et. al2 synthesized and reported eighteen Symmetrical and Unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles and explained Antibacterial activities of derived compounds by invitro studies against four strains of bacteria using agar diffusion technique. The chlorophenicol was taken as a standard drug at same concentration.
3. Nagalakshmi G et. al3 explained Synthesis, Antimicrobial and Anti-inflammatory activity of 2,5-disubstituted-1,3,4-oxadiazoles. The desired compounds were synthesized by the condensation of 4-methoxybenzohydrazide with different aromatic acids in presence of phosphoryl chloride and activity was confirmed.
4. Shashikant R. Pattan et. al4 showed Synthesis of some novel substituted 1,3,4- oxadiazole and pyrazole derivatives and Evaluation for their Anti tubercular activity by comparison with standard drug Streptomycin.
5. Krishna Kant Jha et. al5 explained 3D-QSAR studies of 1,3,4-oxadiazole derivatives as newer Antimycobacterial agents. Various 5-aryl-2-thio-1,3,4-oxadiazole have been reported as good Antimycobacterial agents against Mycobacterium tuberculosis H37RV.
6. Valentine P et. al6 showed synthesis of some substituted 1,2,4-triazo-5-thiono Schiff’s base and explained their Antioxidant activity by Hydrogen Peroxide scavenging method. The desired compound was synthesized from the ester of methyl paraben.
7. Ali Almasirad et. al7 performed synthesis of substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole and explained their Anticonvulsant and Muscle relaxant activities with lesser side effects.
8. Mashooq A Bhat et. al8 synthesized novel 3-(4-acetyl-5H/ methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones and presented them as potential Anticonvulsant agents.
9. Asif Husain et. al9 have reported Synthesis of novel 1,3,4- oxadiazole derivatives and explained the Anti inflammatory, Analgesic and Antibacterial activity of derived compounds. They also mentioned that synthesized compounds were potential for ulcerogenic action.
10. Mohd Amir et. al10 have reported Synthesis of some 1,3,4-oxadiazole derivatives and reported their potential Anti inflammatory activity. Out of synthesized compounds, the compounds which showed good Anti inflammatory activity, were screened for their ulcerogenic and lipid peroxidation activities.
11. Harish Kumar et. al11 explained synthesis and preliminary evaluation of 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid for their biological properties. Some compounds with more Antiinflammatory activity than reference drug was also evaluated.
6.3 – Objective of the Study:-
The present project focuses on the:-
● Synthesis of substituted oxadiazole derivatives.
● Characterisation of synthesized compouds by spectral data (IR, 1HNMR and mass
Spectra).
● Evaluation of synthesized compounds for their:-
1.  Antibacterial activity by Invitro studies.
2.  Antioxidant activity by Invitro studies.
3.  Anti Convulsant activity by Maximal Electroshock-induced Seizure.
Materials and Methods:
7.1- Source of Data:
A-Chemical abstracts & other journals like:-
● Indian Journal of Heterocyclic Chemistry.
● Indian Journal of Chemistry.
● Pharmaceutical Bulletin.
● European Journal of Medicinal Chemistry.
● Indian Journal of Pharmaceutical Sciences.
B- Internet Browsing
7.2 - Method of collection of data:
Chemicals & other reagents will be collected from standard companies. The reactions will be monitored by thin layer chromatography. The products will be purified as per standard protocols. Structure of the synthesized molecules will be confirmed by spectral data.
7.3 - Does the study require any investigations or interventions to be conducted on
patients or other humans or animals? If so, Please describe briefly.
Yes, the study requires investigation on albino rats.
7.4 – Has ethical clearance been obtained from your Institution in case of 7.3?
Yes, the copy is enclosed.
8.0 / List of References:
1. Zuhair Muhi-eldeen, Ghada Juma’a, Elham Al-kaissi and Lina Nouri, Antimicrobial activity of some new Oxadiazole derivatives. Jordan Journal of Chemistry. 2008; 3(3): 233-43.
2. Iqbal R, Zareef M, Ahmed S and Shahzad S. A, A convenient Synthesis and Antibacterial activities of Symmetrical and Unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles. Jour. Chem. Soc., Pak. 2006; 28(2): 165-68.
3. Nagalakshmi G, Synthesis, Antimicrobial and Anti-inflammatory activity of 2,5-disubstituted-1,3,4-oxadiazoles. Indian J Pharm Sci. 2008; 70(1): 49-55.
4. Shashikant R. Pattan, Rabara P A, Wakale V S and Musmade D S, Synthesis and Evaluation of some novel substituted 1,3,4- oxadiazole and pyrazole derivatives for Anti Tubercular activity. Indian J. Chem., Sec.B. 2009; 48: 1453-56.
5. Krishna Kant Jha, Abdul Samad, Yatendra kumar and Sandeep Bansal, 3D-QSAR studies of 1,3,4-oxadiazole derivatives as Anti Mycobacterial agents. Iranian Journal of Pharmaceutical Research. 2009; 8(3): 163-67.
6. Valentine P, Ilango K, Deepthi M and Pavani G, Antioxidant activity of some substituted 1,2,4-triazo-5-thiono Schiff’s base. Journal of Pharmaceutical Sciences and Research. 2009; 1(2): 74-77.
7. Ali Almasirad, Nasim Vousooghi, Sayyed Abbas Tabatabai and Abbas Shafiee, Synthesis, Anticonvulsant and Muscle relaxant activities of substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole. Acta Chem Slov. 2007; 54: 317-24.
8. Mashooq A Bhat, Nadeem Siddiqui and Suroor A Khan, Synthesis of novel 3-(4- acetyl-5H/ methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones as potential Anticonvulsant agents. Acta Poloniae Pharmaceutica- Drug Research. 2008; 65: 235-39.
9. Asif Husain and Mohammed Ajmal, Synthesis of novel 1,3,4- oxadiazole derivatives and their biological properties. Acta Pharm. 2009; 59: 223-33.
10. Mohd Amir, Javed S A and Harish Kumar, Synthesis of some 1,3,4-oxadiazole d derivatives as potential Anti inflammatory agents. Indian J. Chem., Sec.B. 2007; 46: 1014-19.
11. Harish Kumar, Sadique A. Javed, Suroor A. Khan and Mohammad Amir, 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: Synthesis and preliminary evaluation of biological properties. Eur J Med. Chem. 2008; 43(12): 2688-98.
9. / Signature of the candidate /
(ARUN DUREJA)
10. / Remarks of the Guide:
11. / Name and Designation of:
11.1 Guide:
11.2 Signature: / Mrs. Kalpana Divekar
Associate Professor
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.
11.3 Co-Guide:
11.4 Signature / Mr. Pavan Kumar. Puvvada
Senior Lecturer
Dept of Pharmacology
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.
11.5 Head of the Department:
11.6 Signature / Dr. V. Murugan
Professor and principal
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.
12. / 12.1 Remarks of the Chairman and Principal
12.2 Signature
/ Dr. V. Murugan
Professor and principal
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.