New benzochromene-based compounds as potential EGFR-TK inhibitors: synthesis, anti-proliferative activity, molecular docking studies, and ADME profiles

Abstract

In this study, we report the synthesis and biological evaluation of a novel series of benzochromene and benzochromenopyrimidine derivatives employingenaminonitrile compound 1 as a key synthetic precursor. The structures of the synthesized compounds were elucidated using comprehensive analytical and spectroscopic techniques. The antiproliferative activities of the prepared derivatives were evaluated against three cancer cell lines, HCT-116, MCF-7, and HepG2, as well as the normal human lung fibroblast cell line, WI-38, using the MTT assay, with doxorubicin used as the standard reference drug. Among the tested derivatives, compounds 6, 7, and 10 demonstrated notable antiproliferative activity against all examined cancer cell lines. In particular, compound 7 exhibited potent cytotoxic effects, with IC₅₀ values of 5.98, 6.52, and 8.51 µM against HCT-116, MCF-7, and HepG2 cells, respectively, comparable with that of doxorubicin. Importantly, compound 7 displayed low cytotoxicity toward WI-38 cells, resulting in the highest selectivity index (SI = 6.7). Molecular docking analysis further revealed that compound 7 exhibited the promising binding affinity toward EGFR, with a docking score of −9.06 kcal mol⁻¹, comparable with that of gefitinib. Collectively, these findings highlight compound 7 as a potent EGFR-targeting kinase inhibitor with notable anticancer activity.