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

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.