“SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF NOVEL BENZIMIDAZOLE DERIVATIVES”
M.PHARM DISSERTATION PROTOCOL
Submitted to
Rajiv Gandhi University of Health Sciences
Bangalore, Karnataka
By
MOHAMMED WASEEM AHMED
B.Pharm
Under the Guidance of
Dr.Sirajunisa Talath
M.Pharm PhD
Professor
Dept. of Pharmaceutical Chemistry
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
R.M.E.S’s COLLEGE OF PHARMACY,
GULBARGA-585102
2010-2011
Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka
Curriculum Development Cell
Conformation for Registration of
Subjects for Dissertation
Registration No. :
Name of the Candidate : MOHAMMED WASEEM AHMED
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.Pharmacy in Pharmaceutical Chemistry
Date of Admission to the Course : 17/06/2009
Title of the Topic : Synthesis and Antimicrobial Activity
of novel benzimidazole derivatives
Brief resume of the intended work : Attached
Signature of the student :
Guide Name : Dr.Sirajunisa Talath
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 Science, Karnataka Bangalore
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name and Address of the candidate / MOHAMMED WASEEM AHMEDNAV BHARAT METAL CENTRE M.G.ROAD CHOCK BAZAR NANDED (MS) 431604
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 / 17/06/2009
5. / Title of the topic / “Synthesis and antimicrobial activity of novel benzimidazole derivatives”
6. / Brief resume of the intended work:
6.1. Need for the study:
Many important biochemical compounds & drugs of natural origin contain heterocyclic ring structures among these eg. Carbohydrates/ essential amino acids/ vitamins/ alkaloids/ glycosides etc.The presence of heterocyclic structures in such divers types of compounds is strongly indicative of the diverse type of the pharmacological activity & recognition of this is reflected in efforts to find useful synthetics drugs.
The benzimidazole moiety shows pharmacological activities in natural & synthetic compounds some of them show clinical value towards antimicrobial1 ,antiprotozoal2,antibacterial & antifungal activities3, anti inflammatory & analgesic activity4.it also used in treatment of tuberculosis5,cancer6 etc.
The development of resistance to current anti bacterial therapy continues to stimulate the search for more effective agents. The increasing clinical importance of the drug resistant & bacterial pathogens has lent additional urgency to microbiological research and development of novel biologically active compounds hence in present study we planed to synthesize some novel benzimidazoles with good activity and less toxic effects.
6.2 Review of Literature:
Literature survey reveals that the benzimidazole has received considerable attention during last two decades as they are endowed with variety of biological activities and wide range of therapeutic activities. The are few literatures are as under.
· Jin Ru HWV and et.al., were synthesized new benzimidazole-coumarin conjugates & tested for anti-hepatitis C virus agents.7
· Johan Neyts and et.al., for establishment of the structure- activity relationship, heterobicycle-coumarin conjugated compounds with the-SCH2-linker were synthesized & found to possess significant antiviral activity8.
· Katarzyna Kopanska and et.al., were synthesized 1H-benzimidazole & 1H-benztriazole derivatives as inhibitors of acanthamoeba castellanii9.
· K.F.Ansari and et.al., were synthesized some new benzimidazole derivatives & screened for antimicrobial activity.10
· Anthony R.Procari and et.al., were synthesized 1-(substituted benzy)-2-substituted-,6-dichlorobenzimidazoles as nucleoside analogues of 2,5,6-trichloro-1-(b-D-ribofuranosyl)benzimidazole & carried out their antiviral activity.11
· Yoshio Ogino and et.al., were synthesized trans-2-(3-oxospiro[isobenzofuran-1(3H),1`-cyclohexane]-4`-yl] benzimidazole, screened for NPY Y5 receptor antagonist.12
· V.K.Pandey and et.al., were synthesized 8(alkyl,aryl.amido/imido)-7-hydroxy-4-methyl)quinolinyl-[1,5-c]benzimidazoles & carried out their antiviral activity.13
· N.M.Goudgaon and et.al., were synthesized 2-(2-benzylthiopyrimidin4-yl) substituted benzimidazoles & screened for their antimicrobial activity.14
· L.Gurati and et.al., were synthesized some 2-substitued benzimidazole-N-carbamates & screened for antviral activity.14
· N.R.Thimme Gowda were synthesized novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid derivatives & their precursors & carried out the antileukemic agents.16
· Moriana Boiani and et.al., were synthesized second generation of 2-benzimidazole 1,3-dioxide derivatives & screened for their anti-trypanosomatid agents.17
6.3 Objectives:
The increasing clinical importance of drug resistance bacterial and fungal pathogens has lent additional urgency to anti-microbiological research and development and 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 the titled benzimidazole compound.
2. Chemical characterization of newly synthesized compound by I.R.,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 novel benzimidazole 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 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 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 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.
Antimicrobial activity will be carried out by cup plate method or by using micro broth dilution method in our laboratory.
7.3 Does the study require any investigation to be conducted on patients or other humans or animals? If so, please describe briefly.
NOT APPLACABE
7.4 Has ethical clearance been obtained from your institution incase of 7.3
NOT APPLACABLE
8. / List of References
1. Meral Tuncbilec, Tulug Kiper, Nurten Altanlar. Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA.euro.j.of medi.chem.44 (2009) 1024-1033.
2. Hector Torres-Gomez , Emanuel Hernandez-Nunez , Ismail Leon-Rivera , Jorge Guerrero-Alvarez , Roberto Cedillo-Rivera , Rosa Moo-Puc , Rocio Argotte-Ramos , Maria del Carmen Rodriguez-Gutierrez , Manuel Jesus Chan-Bacab , Gabriel Navarrete-Vazquez .Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidin hybrids. bio & med. Chem. Letters 18 (2008) 3147-3151.
3. Hasan kucukbay , Riza Durmaz , Ersin Orhan , Selami Gunal. Synthesis, antibacterial and antifungal activities of electrone-rich olefins derived benzimidazole compounds. Il farmaco 58 (2003) 431-437.
4. Sham M.Sondhi, Nirupma Singh, Ashok Kumar, Olivier Lozach and Laurent Meijer. Synthesis, anti-inflammatory, analgesi and kinase ( CDK-1,CDK-5 AND GSK-3) inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff’s bases.bio. & medi.chem 14 (2006) 3758-3765.
5. Charansingh Gill, Ganesh Jadhav , Mohammad Shaikh Rajesh Kale, Anant Ghwalkar, Deepak Nagaroje , Mahendra Shiradkar. Clubbed [1,2,3] triazoles by fluorine benzimidazole: a novel approach to H37Rv inhibitors as a potential treatment for tuberculosis. Bio.&medi.chem.letters 18(2008) 6244-6247.
6. Thomas D. Penning, Gui-Dong Zhu, Viraj B.Gandhi, Jianchun Gong, Sheela Thomas,wilfried Lubisch , Rland Grandel ,Wolfgang Wernet, Chang H. Park ,Elizabeth H.Fry Xuesong Liu,Yan Shi, Vered Klinghofer Eric F.Johanson ,Cherrie K.Donawho,David J. Frost,Velitchka Bontcheva-Diaz ,Jennifer J.Bouska.Amanda M.Olson,Kennan C.Marsh, Yan Luo, Saul H. Rosenberg , Vincent L.Giranda. Discovery and sar of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide : a potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer.bio.&medi.chem.16 (2008) 6965-6975.
7. Jih Ru Hwu, Raghunath Singha , Shih Ching Hong, Yung Hsiung chang, Asish R. Das, Inge vliegen , Erik De Clercq Johan Neyts. Synthesis of new benzimidazole-coumarin conjugates as anti-hepatitis c virus agents. Antiviral research 77 (2008) 157-162.
8. Johan Neyts , Erik De Clercq , Raghunath Singha , Yung Hsiung chang, asish R. Das, Subhashish K.Chakraborty, Shih Ching Hong, Shwu-chen Tsay, Ming-Hua Hsu, and Jih Ru Hwu. Structuractivity relationship of new anti-hepatitis c virus agents:heterobicycly-coumarin conjugates. J.med.chem.52( 2009 ) 1486-1490.
9. Katarzyna kopanska, Andzelika Najda, Justyna Zebrowska Lidia Chomicz, Janusz Piekarczyk ,Przemyslaw Myjak and Bretner. Synthesis and activity of 1H-benzimidazole and 1H-benzotriazole derivatives as inhibitors of acanthamoeba castellanii. Bio. & medi. Chem.. 12 (2004) 2617-2624.
10. K.F.Ansari, C. Lal. synthesis ,physicochemical properties and antimicrobial activity of some new benzimidazole derivatives. European j.of medi.chem. 44 (2009) 4028-4033.
11. Anthony R.Procari , Rodrigo V.Devivar, Louis S.Kucera. John C drach, and Leroy B. Townsend. Design, synthesis and antiviral evaluations of 1-(substitutedbenzyl)-2-substituted-5,6-dichlorobenzimidazoles as nonnucleoside analogues of 2,5,6-trichloro-1-(b-D-ribofuranosyl)benzimidazole. J.med.chem. 41 (1998) 1252-1262.
12. Yoshio Ogino,Norikazu Ohtake , Yoshkazu nagae, Kenji Matsuda, Makoto Ishikawa, Minoru Moriya, Maki Kanesaka , yuko mitobe , Junko Ito ,Tetsuya kanno. Akane Ishihara, Hisashi Iwaasa, Tomoyuki Ohe, Akio Kanatani, takehiro fukami. Synthesis and structure-activity relationships of novel, potent.and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1`-cyclohexane]-4-yl]benzimidazole NPY Y5 receptor antagonists. Bio. & medi. Chem.. letters 18 (2008) 4997-5001.
13. V.K.Pandey, Zehra Tusi and Sarah Tusi. Synthesis of 8-(alkyl,aryl amido/imido)-7-hydroxy-4-methyl quinolinyl-[1,5-c]benzimidazoles as potential antiviral compounds. Indian journal of heterocyclic chemistry vol.11 aprile-june 2002 ,pp 309-312.
14. N.M.Goudgaon and N.Jeelan Basha. Synthesis and antimicrobial activity of 2-(2-benzylthiopyimidin-4-yl)substituted benzimidazoles. Indian journal of heterocyclic chemistry vol 18,april-june ,2009 pp.353-356.
15. L.Garuti,M.roberti,G.Gentilomi .Synthesis and antiviral assays of some 2-substituted benzimidazole-N-carbamates.il farmaco55(2000) 35-39.
16. N.R.Thimme Gowda, C.V.Kavitha, Kishore K.Chiruvella, Omana Joy, Kanchugarakoppal S.Rangappa, Sathees C. Raghavan. Bio & medi. chem.. letters 19 (2009) 4594-4600.
17. Mariana Boiani ,Lucia Boiani, Alicia Merlino , Paola Hernandez , Agustina Chidichimo, Juan J.Cazzulo, Hugo Cerecetto, Mercedes Gonzalez. European j.of medi.chem.44 (2009) 4426-4433.
9. / Signature of candidate / MOHAMMED WASEEM AHMED
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 / Dr.Sirajunisa Talath M.Pharm Ph.D
Professor
11.2 Signature
11.3 Co-Guide (if any) / …..
11.4 Signature
11.5 Head of the Department / Mr. Kishore Singh C.
M.Pharm (PhD)
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.