Design, synthesis, and apoptotic antiproliferative action of new benzimidazole/1,2,3-triazole hybrids as EGFR inhibitors

Abstract

The research emphasizing hybrids <b>6i</b> and <b>10e</b> for their remarkable activity, with GI₅₀ values of 29 nM and 25 nM, respectively. The inhibitory effects of the most potent hybrids <b>6e</b>, <b>6i</b>, <b>10d</b>, <b>10e</b>, and <b>10g</b> on EGFR were assessed. Compounds <b>6i</b> and <b>10e</b> exhibited greater potency than erlotinib as EGFR inhibitors. Compounds <b>6i</b> and <b>10e</b> were also examined for their apoptotic potential, revealing that these compounds promote apoptosis by activating caspase-3, caspase-8, and Bax, while down-regulating the anti-apoptotic protein Bcl-2. Molecular docking experiments are thoroughly examined to validate the binding interactions of the most active hybrids, <b>6i</b> and <b>10e</b>, with the EGFR active site. Furthermore, our new study examined the ADME properties of the new hybrids.