“SYNTHESIS AND ANTI-BACTERIAL ACTIVITY OF

SOME NOVEL BENZIMIDAZOLE DERIVATIVES”

M. PHARM DISSERTATION PROTOCOL

Submitted to

Rajiv Gandhi University of Health Sciences

Bangalore, Karnataka

By

Mr. SUNIL BHASKAR PULATE

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.

2011-2012

Rajiv Gandhi University of Health Sciences, Karnataka

Bangalore

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name & Address of the candidate / Mr. SUNIL BHASKAR PULATE.
AT-POST-DURGAPUR, TAL- RAHATA, DIST-AHEMADNAGAR, MAHARASHTRA
2. / Name of the Institution / R.M.E.S’s College of Pharmacy, Gulbarga, Karnataka
3. / Course of study and subject / Master of Pharmacy in
Pharmaceutical Chemistry.
4. / Date of Admission to course / 10/7/2010
5. / Title of the Topic / “Synthesis and Anti-bacterial Activity of some Novel Benzimidazole Derivatives.”
6.0
7.0
.
8.0 / BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Many important biochemical compounds and drugs of natural origin contain heterocyclic ring structure. Among these eg: 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 type of the pharmacological activity and recognition of this is reflected in efforts to find useful synthetic drugs.
In the present study, the objective is to synthesize novel compounds from the benzimidazole moiety, recognized for its various biological potentials, Benzimidazole constitute an important and interesting class of heterocyclic compounds, various benzimidazole derivatives possess different pharmacological and biological activities, of which the most potent is anti-fungal 1, anti-bacterial 2, anti-microbial 3, anti-leukemic4, anti-protozoal 5, anti-diabetic6, anti-ulcer 7, anti-inflammatory 8, anti mycobacterial activity9 .
The development of resistance to current antibacterial therapy continuous to stimulate the search for more effective agents, the increasing clinical importance of drug resistant and bacterial pathogens has lent additional urgency to microbiological research and development of novel biologically active compounds. Hence the aim of this work is to synthesize some novel benzimidazole derivative and carry out anti-bacterial potentials with good activity and less toxic effects. The biological activities of the compounds containing basic moiety have been well documented.
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:
 Hasan Kucukbay, et.al., synthesis, antibacterial and Antifungal activities of
electron-rich olefins derived benzimidazole Compounds.10
 A.Khalafi Nezhad, et.al., design ,synthesis, antibacterial and QSAR studies of
benzimidazole and imidazole chloroaryloxyalkyl Derivative.11
 Ilkay Oren, et.al., synthesis and antimicrobial Activity of some novel 2,5 and
/or 6-substituted benzoxazole and Benzimidazole derivative.12
 N.R.Thimme Gowda, et.al., synthesis and biological evaluation Of novel 1-(4-
methoxyphenethyl)-1H-benzimidazole-5-carboxylic acid Derivatives and
their precursors as antileukemic agent.13
 Mariola Andrzejewska, et.al.,synthesis and antiprotozoal And anti- bacterial
activity of 5-substituted 4,6 dibromo and 4,6dichloroMercaptobenzimidazole14
 Ramanatham Vinodkumar, et.al., synthesis ,anti-Bacterial, anti-asthmatic and
anti-diabetic activities of novel N-substituted-2- (4-phenylethynyl-phenyl)-1H
benzimidazoles and N-substituted 2[4-(4,4- Dimethyl-thiochroman-6-yl
ethynyl)-phenyl]-1H-benzimidazole.15
Enzo CEREDA, et.al., anti-secretory and anti-ulcer Activities of some new 2-
(2-pyridylmethyl-sulfinyl)-benzimidazoles.16
Rajiv R. Mohan, et.al., CNS, Anthemintic and anti- Inflammatory activities of
some 1-[2/3-(2-phenyl benzimidazole] 2- Methyl/phenyl-4- (3,4-disubstituted
benzylidene) 5-oxo-imidazole.17
 Z.Kazimierczuk, et.al, synthesis and antimycobacterial activity Of 2-
substituted halogenobenzimidazoles.18
 K.Umaa, et. al., synthesis, characterization and Biological screening of novel
1- substituted benzimidations.19
.S.O.Podunavac-Kuzmanovic,et.al,antibacterial evaluation of
some benzimidazole derivatives and their zinc (11) complexes.20
 Md Salahuddin, et.al, synthesis of some novel thieno [2,3-d] pyrimidines and
their antibacterial activity.21
Bing Qin yang, et.al, synthesis and characterization of novel N-
Ferrocenesulfonyl benzimidazole.22
Anton V. Dolzhenko, et.al, synthesis and dihydrofolate reductase inhibitory
activity of 2-amino-[1,3,5]triazino [1,2-a] benzimidazoles.23
D.N.Patil,et.al, synthesis and antimicrobial activity of some benzimidazole
derivative.24
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 antibacterial 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 anti-bacterial activity.
MATERIALS AND METHODS:
7.1. SOURCE OF DATA:
The present project is synthesis and chemical characterization of some novel benzimidazole derivatives and their antibacterial studies. All chemicals required for 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 METHOD OF COLLECTION 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 recrystallisation techniques. Melting point of the newly synthesized compounds will be analysed by using open capillary tube method.
IR, NMR and Mass spectral data will confirm the chemical characterization of newly synthesized compounds. Anti-bacterial activity will be carried out 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 yours institution in case of 7.3
NOT APPLICABLE
REFERENCES:
  1. Hasan K, Riza D, synthesis, antibacterial and antifungal activities of electron-rich olefins derived benzimidazole Compounds.11Farmaco, 58; (2003): 431-437.
  2. Nezhad AK, Soltani MN , Design ,synthesis, antibacterial and QSAR studies of benzimidazole and imidazole chloroaryloxyalkyl Derivative. Bioorg. and med. chem., 13; (2005): 1931-1938.
  3. Ilkay O, Ozlem T, Ismail Y, Synthesis and antimicrobial Activity of some novel 2,5 and /or 6-substituted benzoxazole and Benzimidazole derivative. Eur. J. Pharm. Sci., (1998): 153-160.
  4. Thimme GNR., Kavitha C, Synthesis and biological evaluation of novel 1-(4-methoxyphenethyl)-1H-benzimidazole-5- carboxylic acid derivatives and their precursors as antileukemic agent. Bioorg. and med. chem. letters, 19; (2009): 4594-4600.
  5. Mariola A, Lilian YM, synthesis and antiprotozoal and anti- bacterial activity of 5-substituted 4,6 dibromo and 4,6 dichloro-2 mercaptobenzimidazole. Eur. J. Pharm. Sci., 21; (2004): 323-329.
  6. Ramanatham V, Sanjay DV, Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N- substituted- 2-(4-phenylethynyl- phenyl)-1H benzimidazoles and N- substituted 2[4-(4,4-dimethyl- thiochroman-6-yl ethynyl)-phenyl]-1H- benzimidazole. Eur. J. med. Chem., 43; (2008): 986-995.
  7. Enzo C, Marco T, Anti-secretory and anti-ulcer activities of some new 2-(2-pyridylmethyl-sulfinyl)-Benzimidazoles. Eur. J. med. chem., 22; (1987): 527-537.
  8. Rajiv RM, Chapla A, CNS, Anthemintic and Anti-inflammatory activities of some 1-[2/3-(2-phenyl benzimidazole] 2- Ethyl/pheny4 (3,4disubstitutedbenzylidene) 5-oxoimidazole. Pharmacological Research Communications, Vol-16, No.4; (1984): 321-338
  9. Kazimierczuk Z, Andrzejewsk M., Synthesis and antimycobacterial activity Of 2-substituted halogenobenzimidazoles. Eur.J. med. Chem., 40; (2005): 203-208.
  10. Umaa K,Krishakumar K & Kannan K, Synthesis, characterization & Biological screening of Novel I-Substituted benzimidations & carried out For Anti-mycobacterial activity,2008; 1(2): 28-33.
  11. Fang.BO, Cheng HZ, Xian-CR, Synthesis and biological activates of novel amine derived bis azoles as potential antibacterial and antifungal agents. Eur. J. medi.chem., 45; (2010): 4388-4398.
  12. Bobba VSK, Sanjay DV, Synthesis and antibacterial activity of some novel 2-(6-fluorochroman-2-yl)-1-Alkyl/acyl/aroyl-1H-benzimidazole. Eur.J. med. Chem., 41; (2006): 599-604.
  13. Sharma P, Kumar A., Synthesis and QSAR studies on 5-[2-(2- Methyl prop 1-enyl)-1H benzimidazole –1 yl]-4, 6 diphenyl-pyrimidin-2-(5H) Thione derivatives as antibacterial agents. Eur. J. Med. chem.., 41; (2006): 833-840.
  14. Ramanatham VK, Sanjay DV, Synthesis, anti- Bacterial, anti-asthmatic and anti-diabetic activities of novel N-Substituted- 2-(4-phenylethynyl-phenyl)-1H benzimidazoles and N-substituted 2[4- (4,4-dimethyl- thiochroman-6-yl ethynyl)-phenyl]- benzimidazole.Eur. J. med.chem., 43; (2008): 986-995.
  15. Mariola A, Lilian YM, Synthesis and Antiprotozoal and anti- bacterial activity of 5-substituted 4, 6 dibromo and 4, 6 dichloro-2-mercaptobenzimidazole. Eur. J. Pharm. chem.., 21; (2004): 323-329.
  16. Sharma S, Saloni G, Convenient one pot synthesis of Novel 2-substituted benzimidazoles, tetrahydrobenzimidazoles and Imidazoles and Evaluation of their invitro antibacterial and antifungal. Activities. Eur. J. med. chem., 44; (2009): 1751-1757.
  17. Yun H, Jun Y, Synthesis and biological evolution of novel Benzimidazoles as potential antibacterial agents. Bioorganic andMed. Chem. letters, 14; (2004): 1217-1220.
  18. Keiji T, Noriaki H, The design and optimization of 2- (Pyridine-2-yl)-1H- benzimidazole compounds as allosteric glucokinase Activators. Bioorg. and Med. Chem.,17; (2009): 7042-7051.
  19. Katarzyna K, Synthesis and activity of 1H-benzimidazole and 1H-Benzotriazole derivatives as inhibitors of Acanthamoeba castellanii.Bioorg. and med. Chem., 12; (2004): 2617-2624.
  20. Podunavac KSO, Cvetkovic DM, antibacterial evaluation of somebenzimidazole derivatives and their zinc (II) complexes.J.serb.chem.soc, 72(5); (2007): 459-466.
  21. Salahuddin Md, sunil k, Synthesis of some novel thieno [2,3-d] pyrimidines and their antibacterial activity.E-J. chem., 6; (2009):801-808.
  22. Bing QY, Peng HY, Synthesis and characterization of novel N-Ferrocenesulfonyl benzimidazole. Chinese chemical letters, 14; (2003):901-903.
  23. Anton VD, Wai KC, Synthesis and dihydrofolate reductase inhibitory activity of 2-amino-[1, 3,5]triazino [1,2-a] benzimidazoles. 9th international electronic conference on synthetic organic chem.,(2005).
  24. Patil. DN, Chaturvedi SC, Kale DL, Synthesis and antimicrobial activityof somebenzimidazole derivative. Continental J. pharm. Sci., 2; (2008): 44-48.

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 and Designation of
(In block letters)
11.1 Guide / PROF.SIDDANNA.A.DURGAD.
M.Pharm (Ph.D)
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, RMES’S COLLEGE OF PHARMACY, GULBARGA-585102
11.2 Signature of guide
11.3 Co-guide (if any) / Mr. HANAMANTH J. KALLUR
M.Pharm
11.4 Signature of co-guide
11.5 Head of the Department / Dr. KISHORE SINGH. CHATRAPATI
M.Pharm Ph.D
PROEFSSOR & HEAD
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY, RMES’S COLLEGE OF PHARMACY, GULBARGA-585102.
11.6 Signature
12. / 12.1 Remarks of the
Chairman & Principal / The above-mentioned information is correct and I recommend the same for approval.
12.2 Signature / Dr. KISHORE SINGH. CHATRAPATI
M.Pharm Ph.D