SYNTHESIS AND STUDY OF ANTI-MICROBIAL ACTIVITY OF SOME NOVEL BENZOXAZOLE DERIVATIVES

M.Pharm dissertation protocol

Submitted to the

Rajiv Gandhi University of Health Science,
Bangalore, Karnataka.

By

Mr. JADHAV RAVIRAJ RAMA

Under the esteemed guidance of

Mr.R.V. HERALAGI

M. pharm.

Asst. Professor

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

B.L.D.E.A’S COLLEGE OF PHARMACY, BIJAPUR

2008-2009

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate & Address
(In block letters) / : / JADHAV RAVIRAJ RAMA
B.L.D.E.A’S. COLLEGE OF PHARMACY,
B.L.D.E. UNIVERSITY CAMPUS,
BIJAPUR.
2. / Name of the Institution / : / B.L.D.E.A’s. COLLEGE OF PHARMACY,
BIJAPUR.
3. / Course of Study and Subject / : / Master of Pharmacy in PHARMACEUTICAL CHEMISTRY
4. / Date of Admission to Course / : / 07-07-2008
5. / Title of the Topic / : / SYNTHESIS AND STUDY OF ANTI-MICROBIAL ACTIVITY OF SOME NOVEL BENZOXAZOLE DERIVATIVES
6. /
Brief resume of the intended work:
6.1 Need for the study :
Many important biochemical compounds and drugs of natural origin contain heterocyclic ring structures. Among these e.g.: carbohydrates, essential amino acids, vitamins, alkaloids, glycosides etc. the presence of heterocyclic structures in such diverse type of compounds is strongly indicative of the diverse types of the pharmacological activity and recognition of this is reflected in efforts to find useful synthetic drugs.
Benzoxazole have received considerable attention during last few decades as they are endowed with variety of biological activities and have wide range of therapeutic properties. Various benzoxazole derivatives possess different pharmacological and biological activities, of which the most potent is anti-inflammatory1, anti-cancer activity2, anti-fungal activity3, anti-microbial activity4, anti-bacterial activity against mycobacterium tuberculosis5.
The development of resistance to current anti-bacterial therapy continues to search for more effective agent. The increasing clinical importance of drug resistance and bacterial pathogens has lent additional urgency to microbiological research and development of novel biological active compound , Hence in the present study we plan synthesize some novel heterocyclic derivatives of benzoxazole with good activity. We are trying to synthesize some novel derivatives with high yield and purity, high potent, and having low side effects.
6.2 Review of literature:
Literature survey reveals that the benzoxazole has received considerable attention during last two decades as they are endowed with variety of biological activities and wide range of therapeutic activities. There are few literatures of benzoxazole are as under.
·  Jarmila Vinsova et.al. Reported anti-microbial activity, after their experiment on synthesis of a series of 2-substituted 5, 7-di-ter-butylbenzoxazole5.
·  Betul Tekiner-Gulbas et.al. reported anti- microbial activity, after synthesis of 2[p-substituted-benzyl]-5-[substituted-carbonylamino] benzoxazoles7.
·  Mreic Kaksal et.al. Reported analgesic and anti-inflammatory activity of some new mannich bases of 5-nitro-2-Benzoxazolines8.
·  Ilkay YILDIZ OREN et.al. Reported microbiological activity after synthesis of some substituted N-(2-hydroxy-4-nitrophenyl) benzamides and phenylacetamides as possible metabolites of antimicrobial active benzoxazoles9.
·  Samia M. Rida et.al., reported anticancer and anti-HIV-1 activity after synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agent2.
·  R. Parammashivappa et.al, Design, synthesis and Biological Evalution of Benzoxazole derivatives as cyclooxygenase Inhibitors10.
·  Chu-Biao Xue et.al, Desing, synthesis and In vitro activities of a series of benzoxazole glycoprotein IIb/IIIa inhibitor11.
Further survey on synthesis of substituted benzoxazole derivatives has also reveled that possessing various biological activities.
6.3  Objectives of the study
1.  Synthesis of some novel type benzoxazole derivatives.
2.  Chemical characterization of the newly synthesized compound by I.R, NMR and Mass spectral data.
3.  To screen the synthesized compound for the anti-microbial activity.
7. / Material and methods:
7.1 Source of data.
The present project is synthesis and chemical characterization of some novel benzoxazole derivatives and their biological evaluation. All chemical required for synthesis were purchase from Aldrich, fluka and SD fine chemicals etc, through college funds. The subject will be studied in detail by referring national and international journals in medicinal chemistry. Our college has E-library facility to browse all the journals.
A}Synthetic strategy :

7.2 Method of collection of data:
The chemical structures of the synthesized compounds will be established on the bases of physical, chemical and analytical data. Purification of the synthesized compounds will be done by using recrystallization 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.
The anti-microbial activity will be carried out by cup plate method or by using micro broth dilution method in laboratory.
7.3: Does the study require any investigations to be conducted on patients or other humans or animals? If so, please describe briefly.
NOT APPLICABLE
7.4 Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
7.2 Method of collection of data:
The chemical structures of the synthesized compounds will be established on the bases of physical, chemical and analytical data. Purification of the synthesized compounds will be done by using recrystallization 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 spectral data.
The anti-microbial activity will be carried out by cup plate method or by using micro broth dilution method in laboratory.
7.3: Does the study require any investigations to be conducted on patients or other humans or animals? If so, please describe briefly.
NOT APPLICABLE
7.4 Has ethical clearance been obtained from your institution in case of 7.3
NOT APPLICABLE
8 / List of References:
1,H. Ozan GULCAN, Serdar UNLU, Erden BANOGLU, M. Fethi SAHIN “Synthesis of New 4-(5-chloro-2-oxo-3H-benzoxazol-3-yl) butanamide Derivatives and their Analgesic and Anti-Inflammatory Properties” Turk J Chem. 27 (2003), 467 - 476.
2. Sumia M.Rida, Fawzia A. Ashour, Soad A.M. El-Hawash, Mona M. Elsemary, et.al. “Synthesis of some novel benzoxazole derivatives as anticancer, Anti-HIV-1 and antimicrobial agent. E. J.Medicinal Chem. 40 (2005) 949 – 959.
3. Elamin I. Elamina, M. Uppal Zuhhir, Abdullah A. Al-Badr “Antibacterial and antifungal
activites of Benzoxazole derivatives”. Antimicrobial agent and chemotherapy.1981, 29-32.
4. P. kohli, S.D.Srivastava and S.K.Srivastava et.al “Synthesis and biological activity of
mercaptobenzoxazole based thiazolidines and their arylidenes” J. chines Chem society, 2007, 54, 1003 – 1010.
5. Jarmila vinsova, Vaclav Horar, Vladimir Buchta, Jarmila Kaustova. “Highly lipophilic benzoxazolea with potential antibacterial activity”. Molecule 2005, 10, 783 – 793.
6. Milan Cacic , Mladen Trkovnik , Frane Cacic and Elizabeta Has-Schon ,”Synthesis and Antimicrobial Activity of Some Derivatives of (7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic Acid Hydrazide” Molecules 2006, 11, 134-147
7. Betul Tekiner-Gulbas, Ozem Temiz-Arpaci, Iikay Yildiz , Nurten Altanlar. “Synthesis and in vitroantimicrobial activity of new 2-[p-substituted-benzyl]-5-[substituted-carbonylamino]benzoxazoles” E.J.Medicinal chem xx (2007) 1 – 7.
8.Meriç Köksal, Nesrin Gökhan1, Esra Küpeli2, Erdem Yesilada, and Hakki Erdogana ”Analgesic and Antiinflammatory Activities of Some New Mannich Bases of 5-Nitro-2-Benzoxazolinones” Arch Pharm Res Vol 30, No 4, 419-424, 2007
9.Ilkay YILDIZ OREN, Esin AKISENER, Cengiz ERTAS,
¨Ozlem TEM_IZ ARPACI, et.al “Synthesis and Microbiological Activity of Some Substituted N-(2−hydroxy-4-nitrophenyl) benzamides and Phenylacetamides as Possible Metabolites of Antimicrobial Active Benzoxazoles” Turk J Chem 28 (2004) , 441 { 449.
10. R. Parammashivappa P.Phani Kumar, P. V. Subba Rao and A. Srinivasa Rao, “Desing, synthesis and Biological Evalution of Benzoxazole derivatives as cyclooxygenase Inhibitors” Bioorganic & medicinal chem. Letters 13(2003) 657-660.
11. Chu-Biao Xue Maria Rafalski, John Roderick, Charles J. Eyermann, Shaker Mousa et al, “Desing , synthesis and In vitro acivities of a series of benzoxazole glycoprotein IIb/IIIa inhibitor” Bioorganic & medicinal chem. Letters,vol.6, no.3, 339-344,1996.
12. Zafer Asim KAPLANICKLI, Gulhan TURAN-ZITOUNI,Gilbert REVIAL, and Kiymet GUVEN. “Synthesis and study of Antibacterial and Antifungal Activities of novel 2-[[(Benzoxazole/benzoxamidazole-2-yl)sulfanyl]acetylamino]thiazoles” Arc pharm Res vol.27, no.11, 1081-1085,2004
13.Özlem Temiz-Arpacia), E. sin Aki-Senera), Ismail Yalçina),Nurten Altanlarb),“Synthesis and Antimicrobial Activity of Some 2-[ p-Substituted-phenyl]benzoxazol-5-ylarylcarboxyamides”Arch. Pharm. Pharm. Med. Chem. 2002, 6, 283–288.
9. / Signature of Candidate / [RAVIRAJ RAMA JADHAV]
10. / Remarks of the Guide / .
11. / Name & Designation of (in block letters)
11.1 / Guide / Mr.R.V. HERALGI
M. Pharm.
Asst. PROFESSOR
DEPT. OF PHARMACEUTICAL CHEMISTRY
B.L.D.E.A. COLLEGE OF PHARMACY, BIJAPUR.
11.2 / Signature
11.3 / Co-Guide: / ---
11.4 / Signature / ---
11.5 / Head of Department / DR. N.V.KALYANE M.Pharm., Ph.D.
PROFESSOR OF PHARMACEUTICAL CHEMISTRY B.L.D.E.A college of Pharmacy , Bijapur
11.6 / Signature
12. / 12.1 / Remarks of the Chairman & Principal
12.2 / Signature /
(Dr.N.V. KALYANE)