“SYNTHESIS AND ANTI MICROBIAL EVALUATION OF
SOME BENZIMIDAZOLE DERIVATIVES”
M.PHARM DISSERTATION PROTOCOL
Submitted to
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
By
K ONKAR
B.Pharm
Under the Guidance of
Prof. SIDDANNA.A.DURGAD
M. Pharm. (Ph.D)
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
RAJIV MEMORIAL EDUCATION SOCIETY’S COLLEGE OF PHARMACY,
GULBARGA-585102
2012-2013
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name and Address of the candidate / K ONKAR,H.NO. 4-8-61/S/3/1,kurihinisetty colony,
Mahabubnagar town,Andhara prasesh,
Pin code 509001.
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 / 22/12/2011
5. / Title of the topic / “SYNTHESIS AND ANTIMICROBIAL EVALUATION OF SOME BENZIMIDAZOLE DERIVATIVES”
6. BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY
In the present study, the objective is to synthesize novel compounds from The Benzimidazole moiety, recognized for its various biological potentials, benzimidazole constitutes an important and interesting class of Hetero cyclic compounds, various Biological Derivatives possess different pharmacological and Biological activities, of which the most potent is antimicrorobial 1, anti mycobacterial activity 2, antileukemic activity 3, antimalarial activity 4, antiulcer 5, anti inflammatory6, antihelmintic activity 7, antiprotozoal activity 8 and antihistaminic activity 9.
Chalcone being a very good synthon was utilized to combine with benzimidazole moiety to design agents with significant anti microbial activity, Benzimidazole is formed when o-phenylene diamine is heated with organic acid i.e formic acid in presence of strong alkali sodium hydroxide it will gives Benzimidazole. Benzimidazole was acetylated with acetyl chloride, the intermediate substituted Chalcones were synthesized from acetylayed Benzimidazole, in order to synthesize different substituted aromatic aldehydes of the basic moiety,1-sub Benzimidazole to obtain different Benzimidazole Derivatives.Their structure were characterized by various spectral techniques like IR ,NMR and Mass. for preliminary screening (antibacterial and antifungal) for antimicrobial activity, the test was performed by disc diffusion assay and determination of minimum inhibitory concentration (MIC) by Broth Dilution method.
The Biological profile of Benzimidazole Derivatives is very extensive. The Benzimidazoles are associated with diverse antimicrobial activities, a large number of Benzimidazoles have been reported to be antifungal, antibacterial and anti leukemic agents,these observation promoted us to synthesize the tittle compound with presumption that incorporation of aromatic aldehydes and Benzimidazole nueclei would produce new compounds with siginificant antibacterial anti fungal properties.
The Development of resistance to current antimicrobial therapy continues to stimulate the search for effective agents; the increasing clinical importance of drug resistant and bacterial pathogens has lent additional urgency to antimicrobial research and development of Biologically active compounds. Hence the aim this work is to synthesize some Benzimidazole derivative and carry out antimicrobial potentials with good activity and less toxic effects.
6.2 REVIEW OF LITERATURE:
Literature survey reveals that The Benzimidazole has received considerable attention during last few decades as they are endowed with variety of Biological activities and wide range of therapeutic properties, there are few literatures of Benzimidazole are as under:
· K.F.Ansari,C.Lal.et.al., synthesized some 1-{[5-(alkyl/aryl)-1,3,4,-oxadiazol-2-yl]methyl}-2-alkyl-1H-benzimidazoles for their antimicrobial activities10.
· NEELA J.DATTA, A.R FARIKH, et.al., synthesized N-(4-acetylpheyl)4-(5-nitro-1H-benzimidazol-2-yl)-benzamide. All compounds have seen evaluated for their antimicrobial & antitubercular activity against different strains of gram positive & negative bacteria & mycobacterium smegmatis species11.
· Ajay Kumar R.,Laizapaul k.,et.al.analysis the drugs susceptibility in mycobacterium tuberculosis using alamar blue assay 12.
· DUBEY K.,Ravi kumar C.,et.al., 1ST Phase synthesis of Benzimidazolones and Benzimidazole chalcones under solvent free conditions 13.
· Meral Tuncbilek Tulug Kiper,et.al., synthesis and invitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against mithicillin resistant Staphylococcus aureus.
· Ghoneim KM, Essawi MY.et.al.,synthesis of 2-[(4-amino or 2,4-diaminophynyl)sulfonyl derivatives of Benzimidazoles,benzothiazole and 6-methyl uracil as potential antimicrobial agents15.
· Z.M.Nofel et.al,synthesized a series of Benzimidazole Schiff’s bases and thiosemicarbazides were synthesized .1-methyl Benzimidazoles and carried out the antimicrobial activities of some newly prepared compounds16.
.
6.3 OBJECTIVES OF THE STUDY
The increasing clinical importance of drug resistant-bacterial and fungal pathogens has lent additional urgency to anti-microbiological research and development of new antimicrobial compounds .Hence we planned in the present objective of the study will be as below.
1) benzimidazole development of the synthetic method for the synthesis of the titled compound.
2) chemical characterization of the newly synthesized compounds by the IR,NMR and MASS spectral
Data.
3) Pharmacological screening for antimicrobial activity.
7 / MATERIAL AND METHOD:
7.1 SOURCE OF DATA:
The present project is synthesis and chemical characterization of some novel benzimidazole derivatives and their antimicrobial studies. all chemicals requires for the synthesis will purchase from Aldrich, Fluka Merk and SD fine chemicals etc. 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 and provide necessary assistance for the student to visit library at IICT Hyderabad and IISC Bangalore for literature survey
7.2 METHODS 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 recrystalization techniques. Melting point of the newly synthesized compound will be analyzed by using open capillary tube method. The chemical characterization of newly synthesized compounds will be confirmed by IR, NMR and Mass spectral data. Antimicrobial activity will be confirmed by cup plate method or by using micro broth dilution method.
7.3 Does the study require any investigation or invention to be conducted on patients or
other humans or animals ?If so please mention 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. Usharani T, Rao M S. and Reddy V.M.Biologically active fused Heterocycles from Naturally occurring Quinines-part II; synthesis of 3-substituted -9-hydroxy-10-undecyl benzo[2131,4,5] thiazolo[2,3-b] benzimidazole-8,11-diones & their Antimicrobial activity.Ind.Jn of Het Chem 1997;6;259-262.
2. K.Umaa,K.Krishakumar & K.Kannan.Synthesis , characterization & Biological screening of Novel I-substituted benzimidation & carried out for Antimycobacterial activity.2008;1(2):28-33
3. Bibhucharan chatterjee.Attempts to find new Anti-malarials part-IV Beta Benziminazolyl ethylamine.J.Che soc; 1929; 2965-2968.
4. Kubo K,Oda, Kaniko T,Satho H,and Nohara A. synthesis of 2-[[4-fluro alkoxy-2-pyridyl]methyl]sulfonyl]-1H benzimidazole as antiulcer agents Chem pharma Bull 1990;38:2853-2858
5. N.R.Thimme Gowda,C.V.Kavitha.Kishore K,chiruvalla,Omana Joy,Kanchugara Koppal S,Rangappa,Sathees C.Raghavan synthesis and biologigal evaluation of novel 1-(4-methoxyphenethyl)-1H benzimidazole -5-carboxylic acid derivatives and their precursors as antileukemic agents.Bioorganic and Medicinal chemistry letters 2009;19;45 94-4600.
6. Sawhwany S.N,Sanjay Bhutani and Dharam Vir.synthesis of some 2-(2-benzimidazolyl)-6-aryl-4, 5-dihydro3(2H)-pyridazinones as potentional antiinflammatory agents.Ind.Jn of chem..1987;26(B):348-350
7. Sanjay Dasharath Vaidya,Bodda Venkata Shiva Kumae,Ramanathan Vinodh Kumar ,Shekhar Baskar Birud & Uday chandrakant Nashelkar.synthesis of some novel N-substituted-2-(Benzo[d]ISOXAZOLE-3-yl methyl)-1H Benzzimidazoles as antihelmintic drugs Ind.in Jn of Het.chem 2005;14;197-200
8. Goel P.Jatav R.K, and Kawathekar N.QSAR and synthesis of 1H benzimidazole derivatives as potent antiprotozoal agents.Ind.Drugs.2007;44(9):664-671.
9. John B Wright Histanine antagonist V some 1-(beta-dimetyamino ethyl)-benzimidazole derivatives.J Am Che soc 1949; 71:2035.
10. K.F.Ansari C. Lal synthesis physicochemical properties and antimicrobial activity of some new benzimidazole derivatives.EUROP.Jn of Med.Chem. 2009;44; 4028-4033.
11. Neela. J. Datta, A.R.Parikh, K.DEO, S.B. Batt and P.N.Kundu. Synthesis and antimicrobial activity of some Benzimidazole. Ind.J.Pharm.Sci.2003;65(1):39-43.
12. Ajay Kumar R, Laizapul K. Analysis of drug Susceptibility in Mycobaterium Tuberculosis using almnar blue assy. Current Science. 2001:80; 72-73.
13. Dubey k., Ravi kumar C.,Babu B.Ist phase synthesis of Benzimidazolones chalcones under solvent-free conditions Ind .Jn of chem..2002; 60(B); 430-432.
14. Meral Tuncbilek,Tulug Kiper,Nurten Atanlar.synthesis and in Vitro Antimicrobial activity of some novel substituted benzimidazole Derivatives Having potent activity against methicillin resistant. Staphylococcus aureus,Europ.Jn of med .chem .2009.2009;44:1024-1033
15. Ghoneim KM.Essawi MY.Mohamed MS.karnal AAM.synthesis of 2-[(4-amino or 2,4-diamino phenyl)sulfonyl Derivatives of Benzimidazole agent.Ind.Jn.che1998;37(B):904-911
16. Nofel ZM,Fahmy HH and Mohamed HS synthesis, antimicrobial agent and molluscidal activities of new benzimidazole derivatives.Arch pharm Res 2002:25(1):28-38
17. Doughari J.H.:Antimicrobial activity of Tamarindous indica:Linn,Trop J Pharm Res.2006,5(2),597-603.
18. Mandal S.C.,Kumar C.K. Majumdar A.,Majumdhar R. and Maity B.C.:2000,71,439-441.
19. Mandal S.C., Nandy A., Pal M .P and saha B.P.: Evaluation of antimicrobial activity of Asparagus racemosus Wild.Root,Phyto Res.200014(2),118-119.
20. Santosh G.N and Paramjyothi S,;in vitro evalution of antimicrobial activity of crude extracts of Launaepinnatifida Cass Leaves, J chem pharma sci,2010,3(2),101-105.
21. National committee for clinical Labarotary standards ,Methods for Dilution antimicrobial
22. National committee for clinical Labarotary standards (NCCLS); 3rd Ed.Approved standard M7-A3, NCCLS, Villanova, A, 1993.
23. Text Book of organic chemistry by I.L.Finar,Vol No 1,4th Edition,666.
9. / Signature of candidate
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 / PROF. SIDDANNA.A.DURGAD
M.Pharm,( Ph.D)
Professor,
Department of Pharmaceutical chemistry,
11.2 Signature of the guide
11.3 Co-Guide (if any) / MR.PRABHUDEV S. MATHAPATI
M.Pharm
Lecturer,
Department of Pharmaceutical chemistry,
11.4 Signature of co-guide
11.5 Head of the Department / dr. KISHORE SINGH.CHATRAPATI
M.Pharm, Ph.D.
11.6 Signature
12. / 12.1 Remark of the Director / principal / The above mentioned information is correct and I recommend the same for approval.
12.2 Signature / PROF. HARIPRASANNA R.C.
M.Pharm,( Ph.D)
Principal,
R.M.E.S’s College OF Pharmacy, Gulbarga 585102.