SYNTHESIS, CHARACTERIZATION AND EVALUATION OF NOVEL 6- SUBSTITUTED BENZIMIDAZOLE-2-CARBAMATES AS POTENTIAL ANTIMICROBIAL AGENTS
Objective: The aim of the present work was to synthesize and characterize a series of 6- substituted benzimidazole-2-carbamic acid derivatives and evaluate them for antimicrobial activity.
Methods: A novel series of 6-substituted benzimidazole-2-carbamic acid derivatives (6a-f) were synthesized by reacting substituted benzyl chlorides (2a-c) with 4-hydroxy -2- nitro aniline (3) in the presence of anhydrous K2CO3 in acetone. The series of 4-benzyl oxy -2-nitro anilines (4a-c) thus obtained were reduced with Raney nickel as catalyst. The 4-substituted-1, 2-phenylene diamines were then reacted with 1, 3- bis (alkoxy carbonyl)-S-methyl isothiourea (5a-b) to yield the final compounds (6a-f). The structures of synthesized compounds were established by 1H NMR and mass spectroscopy. The synthesized compounds were screened for antibacterial and antifungal activity against five pathogenic bacterial strains and two pathogenic fungal strains.
Results: All compounds showed moderate to good antibacterial and antifungal activity and were nearly effective as the standard antibacterial and antifungal drugs used for comparison. The exhibited good activity against gram negative bacterial strains like K. pneumoniae and P. aeruginosa as well as against fungal strain C. albicans.
Conclusion: The Â 6-substituted benzimidazole-2-carbamates. compounds synthesized and evaluated for pharmacological activity are promising as antimicrobial agents and are amenable for further optimization.
2. Srikanth L, Raj VV, Raghunandan N, Venkateshwerlu L. Recent advances and potential pharmacological activities of benzimidazole derivatives. Der Pharm Chem 2011;3(2):172-93.
3. Desai JV, Chavan RS, Chaudhari NS, Patil ST. A short review on chemistry and potential activities of benzimidazole molecule. Int J Pharm Tech 2013;5(1):2477-94.
4. Malathi R, Viswanathan CL. Benzimidazole-2-Carbamic acid as a privileged scaffold for antifungal, anthelmintic and antitumor activity: A review. Int J Pharm Pharm Sci 2014;6(5):17-25.
5. http: //www. google. com/patents/US3010968 (accessed Apr 20, 2014).
6. http: //www. google. com/patents/US3370957 (accessed Apr 20, 2014).
7. Chemspider database. CSID: 23741, http: //www. chemspider. com/Chemical-Structure. 23741. Html (accessed 9:55, Apr 20, 2014).
8. Chemspider database. CSID: 26771, http: //www. chemspider. com/Chemical-Structure. 26771. Html (accessed 10:00, Apr 20, 2014).
9. Chemspider database. CSID: 31583, http: //www. chemspider. com/Chemical-Structure. 31583. Html (accessed 10.05, Apr 20, 2014).
10. Ireland CM, Gull K, Gutteridge WE, Pogson CI. The interaction of benzimidazole carbamates with mammalian microtubule protein. Biochem Pharmacol 1979;28:2680-82.
11. Kazimierczuk Z, Upcroft JA, Upcroft P, Gorska A, Starosciak B, Laudy A. Synthesis, antiprotozoal and antibacterial activity of nitro-and halogeno-substituted benzimidazole derivatives. Acta Biochim Pol 2002;49(1):185-95.
12. Panneer Selvam T, Radhika PP, Janagaraj S, Siva Kumar A. Synthesis of novel 2-substituted benzimidazole derivatives as potential antimicrobial agents. Res Biotechnol 2011;2(3):50-7.
13. Sudheer Babu I, Selvakumar S, Manasa GM, Haritha P, Neeraja B, Basri RS, et al. Synthesis, characterization and antimicrobial screening of some 1-substituted benzimidazole derivatives. Int J Pharm Ind Res 2012;2(1):71-7.
14. Mehendale NP, Gowsa PT. Synthesis and antifungal activity of some substituted benzimidazole analogues. Int Res J Pharm 2012;3(7):189-94.
15. http: //www. google. com/patents/US3657267 (accessed Apr 22, 2014).
16. http: //www. google. com/patents/US3812173 (accessed Apr 23, 2014).
17. Townsend LB, Wise DS. The synthesis and chemistry of certain anthelmintic benzimidazoles. Parasitol Today 1990;6(1):107-12.
18. Nikam SR, Khanvilkar VV, Jagdale DM, Jadhav AP, More SH, Kadam VJ. Evaluation of antibacterial and antifungal activities of marketed anti-dandruff shampoos. Indo Am J Pharm Res 2013;3(10):8097-100.
19. Raghavendra KR, Ajay Kumar K, Shashikanth S. Synthesis of novel 1,4-Benzothiazepines and in vitro screening of their antimicrobial activity. Int J Pharm Pharm Sci 2014;6(5):90-3.
20. Varshney S, Saxena V. Design, Synthesis, characterization and biological evaluation of some novel cinnolo piperazine derivatives. Int J Pharm Pharm Sci 2014;6(5):245-8.