IMB5046, a microtubule inhibitor discovered by our team, served as the lead compound for designing a series of selenium-containing benzoates and benzamides. Among these, compound 2g emerged as a lead candidate, demonstrating potent antiproliferative activity. Mechanistic studies revealed that 2g bound to the colchicine site of tubulin, caused G2/M cell cycle arrest, and generated ROS. Notably, 2g exhibited exceptional efficacy in P-gp overexpressing MCF7/ADR and KB