Integrated in vitro and in silico evaluations of novel benzanilide derivatives as anticancer agents.

AIMS: This study aimed to design, synthesize, and evaluate novel benzanilide derivatives as potential anticancer agents targeting VEGFR-2-mediated tumor angiogenesis.

MATERIALS AND

METHODS

Eight benzanilide derivatives (7a-e, 9a-b, and 11) were synthesized and structurally confirmed using spectroscopic methods. The compounds were evaluated via molecular docking, in silico ADMET profiling, in vitro cytotoxicity against MCF-7, MDA-MB-231, HepG-2, and HCT-116 cancer cell lines, and selectivity assessment using WI-38 and WISH normal cell lines. VEGFR-2 enzyme inhibition was also determined for the most active compound.

RESULTS

Compound 11 exhibited the highest cytotoxic activity with IC50 values of 6.08, 5.76, 7.94, and 4.64 µM against MCF-7, MDA-MB-231, HepG-2, and HCT-116, respectively, comparable to sorafenib. It showed potent VEGFR-2 inhibition (IC50 = 0.414 µM) superior to sorafenib (0.809 µM). Mechanistic studies indicated activation of apoptosis via upregulation of Bax, Caspase-3, and Caspase-8 and downregulation of Bcl-2. ADMET results revealed favorable pharmacokinetic properties and acceptable safety profiles.

CONCLUSIONS

Compound 11 represents a promising VEGFR-2 inhibitor with potent anticancer activity and favorable drug-like properties, warranting further optimization and development.