Organoselenium-based Schiff bases and amidic acid derivatives as promising anticancer agents targeting breast cancer by downregulating BCL-2: design, synthesis, and biological evaluation

), 13.50 µM (A549), and 31.28 µM (HEPG2), significantly outperforming doxorubicin across multiple cell lines. Importantly, HB183 showed selective cytotoxicity with lower GI% values against normal OEC (53.90%) and HSF (42.27%) cells. Mechanistic investigations revealed that HB183 upregulated key pro-apoptotic proteins-BAX (1.39-fold), caspase-3 (1.18-fold), caspase-7 (1.20-fold), and caspase-9 (1.45-fold)-while downregulating anti-apoptotic markers such as BCL-2 (1.22-fold), MMP2 (1.15-fold), and MMP9 (1.30-fold). Furthermore, flow cytometry analysis indicated that HB183 induced cell cycle arrest at the pre-G1 phase in MCF7 cells, increasing the population from 94.32% to 98.84%. Molecular docking, molecular dynamics simulation (for 500 ns), and MM-GBSA calculations for the lead analogue (HB183) towards the BCL-2 target, as a crucial one in the pathway of apoptosis induction, were performed to support the mechanistic investigation. These findings suggest that HB183 is a promising lead for further development as a selective and potent anticancer agent, particularly in the treatment of breast cancer.