SYNTHESIS, CHARACTERIZATION AND IN VITRO ANTIMICROBIAL EVALUATION OF SOME NOVEL BENZIMIDAZOLE DERIVATIVES BEARING HYDRAZONE MOIETY
Objective: The synthesis of novel benzimidazole-hydrazone derivatives has been carried out based on the previous findings that both these pharmacophores possess potent antimicrobial activities. The antibacterial properties of synthesized derivatives were screened against both Gram-positive and Gram-negative bacteria.
Methods: O-phenylenediamine on condensation with substituted aromatic acids in polyphosphoric acid gave benzimidazole nucleus which on reaction with ethyl chloroacetate and hydrazine hydrate in two different steps resulted in the formation of substituted acetohydrazides. The targeted compounds 6a-l were synthesized by reaction of substituted acetohydrazides with aromatic aldehydes and screened for their antibacterial potential by cup-plate method.
Results: The synthesized benzimidazole-hydrazones exhibited moderate to strong antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The compounds 6a-6f were found to be most effective against S. aureus, E. coli, and P. aeruginosa. Among all the synthesized compounds, the zone of inhibition of 6f in highest concentration, i.e., 100 Î¼g/ml were found to be >31 mm against all the stains of bacteria.
Conclusion: The antibacterial results revealed that the synthetized derivatives have significant antimicrobial properties and further structure activity relationship studies may develop more potent and less toxic molecules.
2. Rai J, Randhawa GK, Kaur M. Recent advances in antibacterial drugs. Int J Appl Basic Med Res 2013;3:3-10.
3. Sharma A. Antimicrobial resistance: No action today, no cure tomorrow. Indian J Med Microbiol 2011;29:91-2.
4. While A. No action today means no cure tomorrow: The threat of antimicrobial resistance. Br J Community Nurs 2016;21(7):344-7.
5. Santhanamari TH, Meenakshi PR, Velayutham SR. In vitro antibacterial activity of extracts of Lawsonia inermis and Punica grantum against clinically isolated antibiotic resistant Pseudomonas aeruginosa and Staphylococcus aureus. Asian J Pharm Clin Res 2011;4:62-5.
6. Zhang D, Wang Z, Xu W, Sun F, Tang L, Wang J. Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles. Eur J Med Chem 2009;44(5):2202-10.
7. Marinescu M, Tudorache DG, Marton GI, Zalaru CM, Popa M, Chifiriuc MC, et al. Density functional theory molecular modeling, chemical synthesis, and antimicrobial behavior of selected benzimidazole derivatives. J Mol Struct 2017;1130:463-71.
8. Sharma D, Narasimhan B, Kumar P, Jalbout A. Synthesis and QSAR evaluation of 2-(substituted phenyl)-1H-benzimidazoles and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones. Eur J Med Chem 2009;44:1119-27.
9. Apohan E, Yilmaz U, Yilmaz O, Serindag A, KÃ¼Ã§Ã¼kbay H, Yesilada O, et al. Synthesis, cytotoxic and antimicrobial activities of novel cobalt and zinc complexes of benzimidazole derivatives. J Organomet Chem 2017;828:52-8.
10. Zhu W, Da Y, Wu D, Zheng H, Zhu L, Wang L, et al. Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT 1 antagonists with anti-hypertension activities. Bioorg Med Chem 2014;22:2294-302.
11. Bansal Y, Silakari O. The therapeutic journey of benzimidazoles: A review. Bioorg Med Chem 2012;20(21):6208-36.
12. Lavanya P, Suresh M, Kotaiah Y, Harikrishna N, Rao CV. Synthesis, antibacterial, antifungal and antioxidant activity studies on 6-bromo- 2-substitutedphenyl-1H-imidazo [4,5-b] pyridine. Asian J Pharm Clin Res 2011;4:69-73.
13. Tonelli M, Novelli F, Tasso B, Vazzana I, Sparatore A, Boido V, et al. Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents. Bioorg Med Chem 2014;22:4893-909.
14. Gaba M, Gaba P, Uppal D, Dhingra N, Bahia MS, Silakari O, et al. Benzimidazole derivatives: Search for GI-friendly anti-inflammatory analgesic agents. Acta Pharm Sin B 2015;5:337-42.
15. Achar KC, Hosamani KM, Seetharamareddy HR. In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur J Med Chem 2010;45(5):2048-54.
16. Roopashree R, Mohan CD, Swaroop TR, Jagadish S, Rangappa KS. Synthesis, characterization, and in vivo biological evaluation of novel benzimidazoles as potential anticancer agents. Asian J Pharm Clin Res 2014;7:309-13.
17. Da Settimo A, Primofiore G, Da Settimo F, Calzolari L, Cazzulani P, Passoni A, et al. 1-Substituted 2-benzylaminobenzimidazole derivatives: Compounds with H1-antihistaminic activity. Eur J Med Chem 1992;27:395-400.
18. Cereda E, Turconi M, Ezhaya A, Bellora E, Brambilla A, Pagani F, et al. Anti-secretory and anti-ulcer activities of some new 2-(2-pyridylmethyl-sulfinyl)-benzimidazoles. Eur J Med Chem 1987;22:527-37.
19. TunÃ§bilek M, Kiper T, Altanlar N. Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA. Eur J Med Chem 2009;44(3):1024-33.
20. Bui HT, Ha QT, Oh WK, Vo DD, Chau YN, Tu CT, et al. Microwave assisted synthesis and cytotoxic activity evaluations of new benzimidazole derivatives. Tetrahedron Lett 2016;57:887-91.
21. Wen J, Luo YL, Zhang HZ, Zhao HH, Zhou CH, Cai GX. A green and convenient approach toward benzimidazole derivatives and their antimicrobial activity. Chin Chem Lett 2016;27:391-4.
22. Mehranpour AM, Zahiri M. Synthesis and characterization of new benzimidazole derivatives using 2-substituted 1,3-bis(dimethylamino)- trimethinium salts. Tetrahedron Lett 2014;55:3969-71.
23. Fang XJ, Jeyakkumar P, Avula SR, Zhou Q, Zhou CH. Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents. Bioorg Med Chem Lett 2016;26(11):2584-8.
24. Asif M, Husain A. Analgesic, anti-Inflammatory, and antiplatelet profile of hydrazones containing synthetic molecules. J Appl Chem 2013. DOI: 10.1155/2013/247203.
25. Popiolek L. Hydrazide-hydrazones as potential antimicrobial agents: Overview of the literature since 2010. Med Chem Res 2017;26(2):287-301.
26. Soltani Rad MN, Khalafi-Nezhad A, Behrouz S. Synthesis of some novel hydrazono acyclic nucleoside analogues. Beilstein J Org Chem 2010;6:49.
27. Malik MA, Al-Thabaiti SA, Malik MA. Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones. Int J Mol Sci 2012;13:10880-98.
28. Ã–zkay Y, Tunali Y, Karaca H, Isikdag I. Antimicrobial activity of a new series of benzimidazole derivatives. Arch Pharm Res 2011;34(9):1427-35.
29. Hein DW, Alheim RJ, Leavitt JJ. The use of polyphosphoric acid in the synthesis of 2-aryl-and 2-alkyl-substituted benzimidazoles, benzoxazoles and benzothiazoles1. J Am Chem Soc 1957;79:427-9.
30. Paul K, Bindal S, Luxami V. Synthesis of new conjugated coumarin-benzimidazole hybrids and their anticancer activity. Bioorg Med Chem Lett 2013;23(12):3667-72.
31. Ansari KF, Lal C. Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents. Eur J Med Chem 2009;44(5):2294-9.
32. Shaharyar M, Mazumder A, Ahsan MJ. Synthesis, characterization and anticancer evaluation of 2-(naphthalen-1-ylmethyl/naphthalen- 2-yloxymethyl)-1-[5-(substituted phenyl)-[1, 3, 4] oxadiazol-2- ylmethyl]-1H-benzimidazole. Arab J Chem 2014;7:418-24.
33. Shaharyar M, Mazumder A, Abdullah MM. Synthesis, characterization and antimicrobial activity of 1, 3, 4-oxadiazole bearing 1H-benzimidazole derivatives. Arab J Chem 2017;10:S503-8.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.