Synthesis, Cytotoxicity, and Docking Studies of Novel Chalcones Incorporating 2‐(1 H ‐Indol‐1‐yl)‐ N ‐arylacetamide and Benzo[ d

ABSTRACT

A new series of benzothiazole–chalcone–indole N ‐arylacetamide hybrids ( 7a–e ) was designed, synthesized, and spectroscopically characterized as potential anticancer agents. Their antiproliferative activity was evaluated by MTT assay against HCT‐116, MCF‐7, HepG2, and Hep2 cancer cell lines, alongside normal WI‐38 fibroblasts. Compounds 7a and 7d exhibited the most potent and selective cytotoxicity, with low‐micromolar IC ₅₀ values and selectivity indices exceeding that of doxorubicin. Lead compound 7a significantly induced apoptosis and cell‐cycle arrest in MCF‐7 cells, as evidenced by increased apoptotic fraction, elevated sub‐G1 content, and accumulation of cells in the G2/M and S phases. It also showed strong antioxidant activity comparable to vitamin C. Mechanistic studies revealed upregulation of Bax, caspase‐3, ‐8, and ‐9, a slight reduction in Bcl‐2 and CDK expression, suggesting involvement of both intrinsic and extrinsic apoptotic pathways. Molecular docking predicted favorable binding of compound  7a to BRAF, CDK6, EGFR, and c‐MET kinases, supporting its multitarget potential. Overall, compound 7a represents a promising multitarget anticancer lead for further optimization.