Synthesis, Anti-HIV, Antimicrobial Evaluation and Structure Activity Relationship Studies of Some Novel Benzimidazole Derivatives

Abstract

In this study 26 novel benzimidazole compounds bearing alkyl chain as linker at N-1 position were synthesized and evaluated to investigate their possible anti-HIV and antimicrobial activities. Structures of the synthesized compounds were elucidated by spectral data. HIV-1 RT inhibitory activity was evaluated by using HIV-1 RT RNA-dependent DNA polymerase activity assay. Among these derivatives, compounds 43, 45, 50 and 51 were found to have reasonable HIV-1 RT inhibitory activity while the rest exhibited weak activity in comparison to the standard efavirenz. On the other hand, most of the test compounds were found to be significantly effective against gram positive bacteria (Staphylococcus aureus and Bacillus subtilis) and some gram-negative bacterial strains (Escherichia coli, Salmonella typhi, Klebsiella pneumoniae and Pseudomonas aeruginosa), among which compounds 37, 43, 45, 50 and 51 surfaced out as the most effective antibacterials but less effective than the standard ciprofloxacin. Compounds 33, 41 and 47 also showed significant activity against almost all the bacterial strains while all other compounds showed moderate activity towards all the bacterial strains. In case of fungal strains like Candida albicans and Aspergillus niger, almost all the compounds were found to exhibit potency comparable or more than that of standard drug fluconazole except for the compounds 34, 39, 42, 47 and 48 which exhibited moderate to good activity against both the fungal strains. A structure activity relationship (SAR) as well as virtual ADME and toxicity prediction were carried out and a connection between activities, electronic, physicochemical properties and toxicity levels of the target compounds was determined. Keywords: ADME, antibacterial activity, antifungal activity, anti-HIV activity, benzimidazole, SAR, toxicity prediction.