In Vitro and In Silico Evaluation of Anticancer Potential and Apoptotic Activity of Benzimidazole‐Based Compounds

Abstract In this study, two series of benzimidazole derivatives were evaluated for their anticancer activity. The first series of benzimidazole–urea was achieved from the condensation of benzimidazole aniline 1 with a variety of isocyanates. The second series was elaborated from the cycloaddition reaction of benzophenone diamine with appropriate arylaldehydes. The in vitro cytotoxic and antiproliferative properties of various benzimidazole derivatives were assessed for three specific cancer cell lines: MCF‐7, HCT116, and HePG2. Particularly, the results revealed that compounds 6b and 6c exhibited excellent activity against the three cancer cell lines, MCF‐7, HePG2, and HCT‐116, with IC 50 ranging from 0.3 ± 0.01 to 0.1 ± 0.02 µg/mL for MCF‐7, 0.5 ± 0.1 to 0.3 ± 0.1 µg/mL for HePG2, and 0.2 ± 0.01 to 0.06 ± 0.001 µg/mL for HCT‐116. The existence of the hydroxyl and bromine moiety at the para position, the appropriate bromine radius ( r (Br) = 1.83 Å) for derivative 6b , and the hydroxylated group ( r (O) = 1.52 Å for oxygen) for compound 6c were taken into consideration when interpreting this finding. The docking analysis demonstrates that compounds 3e, 6b, 6c , and 6e interact with key residues in the catalytic region of caspase 3, a crucial enzyme involved in apoptosis.