Discovery of Novel Diaryl-Substituted Fused Heterocycles Targeting Katanin and Tubulin with Potent Antitumor and Antimultidrug Resistance Efficacy

Disrupting microtubule dynamics has emerged as a promising strategy for cancer treatment. However, drug resistance remains a challenge hindering the development of microtubule-targeting agents. In this work, a novel class of diaryl substituted fused heterocycles were designed, synthesized, and evaluated, which were demonstrated as effective dual katanin and tubulin regulators with antitumor activity. Following three rounds of stepwise optimization, compound