Design, Synthesis, and in-silico Studies of New Disubstituted Benzimidazoles: Evaluation of In-vitro Anticancer and Antimicrobial Activity

Abstract

A series of thirteen new benzimidazole scaffolds 4(a-m) was synthesized by nucleophilic substitution of 2-chloro- N-(aryl)-acetamides 3(a-m) with 2-(substituted phenyl)-1H-benzo[d]imidazoles 2(a-e) in N.N-Dimethylformamide. All the synthesized compounds were tested on the MCF-7 cell line, followed by antibacterial and antifungal activity. The anticancer activity was determined using MTT assay technique, whereas the antimicrobial activity was carried out using two-fold serial dilution technique. Among all the tested compounds, compound 4b exhibited the highest anticancer and antimicrobial activity, comparable to the standard drug. Finally, the binding mode analysis of the highly active compounds was performed at the active binding sites of the co-crystallized structure of the MCF-7 cell line (PDB ID 1ZXM) and glucosamine-6-phosphate synthase (PDB ID 2VF5). In silico absorption, distribution, metabolism, and excretion studies were also carried out.. KEYWORDS :Benzimidazoles, Cytotoxicity, in silico studies, MCF-7 cell lines, MTT assay.