Design, synthesis, anticancer activity and molecular docking of novel 1H-benzo[d]imidazole derivatives as potential EGFR inhibitors

Abstract

Here, we present the design, synthesis, and evaluation of a new series of 1H-benzo[d]imidazole derivatives (10a–j) to determine their anticancer efficacy. The MCF-7 and HCT116 cancer cell lines were used to test the synthesized compounds anticancer effects. Most of the newly synthesized benzimidazole compounds had a cytotoxic impact, in some cases much more potent than the reference medication. When compared to the reference drug erlotinib, compounds 10g, 10i, and 10j in particular shown strong anticancer efficacy against the tested cancer cell lines with good safety and selectivity indices. All newly synthesized compounds relative inhibitory potency against EGFR wild type (WT) and mutant EGFR L858R/T790M was evaluated in comparison to erlotinib, a standard drug. Comparing compound 10i to other members of the series, it showed the most inhibitory effect against EGFR WT and L858R/T790M with IC50 values of 4.38 and 5.69 nM, respectively. Synthetic compounds revealed substantial EGFR WT and L858R/T790M inhibition with selectivity of over 3.09 and 13.29-folds greater activity than reference medication erlotinib. One such example is compound 10i. The mode of action mechanisms between the potent molecules and the matching EGFR kinase protein were explained by molecular docking investigations. Additionally, predicting the drug-likeness of molecules were promising, indicating the compounds’ drug-like characteristics. Compounds 10g, 10i, and 10j have been shown to be good candidates and deserving further exploration.