ABSTRACT Colchicine binding site inhibitors (CBSIs) have developed rapidly in recent years as antitumor agents. Currently, no inhibitors of this specific class are approved for clinical use. In this study, a series of novel 2‐trifluoromethyl‐4‐aminoquinoline derivatives were designed, synthesized, and evaluated for their antiproliferative activity. Among them, compound 8a was the most potent against LNCaP cells with an IC 50 value of 1 nM. Mechanistic studies demonstrated that 8a disrupted tubulin polymerization by binding to the colchicine site of tubulin. Meanwhile, 8a could induce cell apoptosis. Molecular docking indicated that 8a could bind well to the amino acid residues in microtubule protein cavities. Overall, these findings suggested that compound 8a could be a promising antitumor agent targeting the tubulin colchicine binding site.
Kong et al. (Mon,) studied this question.