A new series of benzimidazole–oxadiazole-small molecules were synthesized and confirmed with various spectroscopic
techniques. The prepared derivatives exhibited significant inhibitory activity against the proliferation
of different cancer cells. The benzimidazoles 10f, 10 h, 10 g, and 10i showed broad anticancer activity with no
selectivity in five-dose assays. All prepared compounds displayed potent inhibitory activity against proliferation
of a panel of four human cancer cells (HT-29, Panc-1, MCF-7, and A-549) with IC50 values ranging from 24 nM to
80 nM and with significant safety profile against MCF-10 A normal cells. According to the mechanistic study, the
most potent compounds (9a, 9b, 10e, 10f, & 10i) displayed remarkable inhibitory effectiveness against EGFR
and BRAFV600E and were more potent than reference drugs erlotinib and vemurafenib. Molecular docking study
for compounds 9a, 9b, 10e, 10f, and 10i agreed with mechanistic results.