Synthesis, Biological Evaluation, and In Silico Analysis of Benzothiazolyl-Furano Thiazolidinones as Tubulin Polymerization Inhibitors.

A novel series of benzothiazole-based furanylthiazolidinone derivatives was designed, synthesized, and biologically evaluated to explore their anticancer potential against triple-negative breast cancer (TNBC). A total of 34 compounds were prepared and screened for in vitro cytotoxic activity against MDA-MB-231 cell lines, along with selectivity assessment in normal HEK-293 cells. Among them, compounds 8j and 8k exhibited the most potent cytotoxic effects, with IC50 values of 5.57 and 7.48 µM, respectively, while demonstrating minimal toxicity toward normal cells. Mechanistic investigations revealed that these compounds induce apoptosis and inhibit tubulin polymerization in a dose-dependent manner, suggesting a microtubule-targeting mode of action. Molecular modeling studies, including binding free energy calculations, further confirmed their strong and stable interactions at the colchicine-binding site of tubulin. In addition, ADME/T predictions indicated favorable pharmacokinetic profiles, including good oral absorption and acceptable drug-likeness. Overall, this study highlights benzothiazole-based furanylthiazolidinones, particularly compounds 8j and 8k, as promising lead candidates for further development as anticancer agents targeting TNBC.