Design, synthesis and bioevaluation of novel trifluoromethylquinoline derivatives as tubulin polymerization inhibitors

Aim: A series of novel trifluoromethylquinoline derivatives were designed, synthesized and evaluated for antitumor activities. Methodology: All compounds were evaluated for antiproliferative activity against four human cancer cell lines. Results: Among them, 5a, 5m, 5o and 6b exhibited remarkable antiproliferative activities against all the tested cell lines at nanomolar concentrations. Mechanism of action studies demonstrated that 6b targeted the colchicine binding site, potentially inhibiting tubulin polymerization, and further studies indicated that 6b could arrest LNCaP cells in the G2/M phase and induce cell apoptosis. Molecular docking confirmed that 6b could bind to the colchicine binding site. Conclusion: Results suggested that 6b could serve as a promising lead compound for the development of novel tubulin polymerization inhibitors and cancer therapy. I am very sorry for that we made a mistake in the above Graphical abstract that the N atom of quinoline ring is missing in the structure of the compound 6b. It is still not be corrected, could you please correct it for us by replacing the CH with N in the structure of the compound 6b. !!!!! When you finished the corrections please delete this paragraph.

Automated summary

A series of novel trifluoromethylquinoline derivatives were synthesized and evaluated for their antitumor activities. Compound 6b was found to exhibit remarkable antiproliferative activities across multiple cell lines, potentially inhibiting tubulin polymerization through targeting the colchicine binding site. Docking studies confirmed the binding of compound 6b to the colchicine binding site.