Synthesis and in vitro biological evaluation of (iso)quinoline-1,2,3-triazole derivatives as anticancer agents

Two series of triazole derivatives were designed and synthesized as potential anticancer agents. A series of eighteen novel 1,2,3-triazole derivatives were synthesized through copper catalyzed click reaction. The compounds were evaluated for their cytotoxicity activity against HepG2, HeLa cell and HEK293 cell lines using MTT assay. The results showed that compounds 10 and 11 were the most potent compounds against HepG2 cell with IC 50 values 9.6 and 13.3 μM, respectively. Additionally, the compounds 10 and 11 were the most potent compounds against HeLa cell with IC 50 values 5.7 and 5.8 μM, respectively. The results of tubulin polymerization assay demonstrated that lead compound 2 and compound 10 could inhibit in vitro tubulin polymerization. In addition, a mechanism study displayed that 10 blocked cell cycle arrest at G2/M phase. Furthermore, a molecular docking study demonstrated that 10 can bind to the colchicine site of tubulin and form hydrogen bonds in the active site of β-tubulin. In summary, our study recommends a promising isoquinoline-triazole scaffold for further development as more efficient microtubule polymerization inhibitors in the field of cancer treatment. Graphical abstract