Nicotinonitrile based dual inhibitors of tubulin and topoisomerase II exhibit potent anticancer activity

This study describes the synthesis of novel pyridine-based derivatives through a series of chemical reactions including chlorination, cyclization, and azidation. The structures of the synthesized compounds were confirmed using different spectroscopic techniques and supported by DFT calculations.The compounds were evaluated for their cytotoxic activity against breast, liver, and colon cancer cell lines, showing dose-dependent inhibition with low toxicity toward normal cells. The strongest activity was observed against breast cancer cells. Additional studies revealed that some compounds act as dual inhibitors of tubulin polymerization and topoisomerase II. In particular, compounds 20 and 37 showed the highest activity, suggesting their potential as promising anticancer agents.