Concise synthesis and preliminary biological evaluation of new triazolylthioacetone derivatives bearing pyridine, pyrazine, and 3,4,5-trimethoxybenzyl fragment

摘要

Based on our previous work, a series of novel triazolylthioacetones incorporating pyridine, pyrazine, and 3,4,5trimethoxybenzyl fragment were synthesized, and evaluated for antiproliferative activities and interactions with tubulin. Some analogues exhibited moderate to excellent potency, with the most promising compound IIc possessing IC50 values of 0.62, 1.46, and 3.65 mu M against HT-29, HCT116, and HepG2 tumor cells, respectively, which were comparable with the positive control CA-4. Mechanistical studies revealed that IIc concentrationdependently caused cell cycle arrest at the G2/M phase in HCT116 tumor cells, and displayed a significant inhibition of tubulin polymerization with an IC50 value of 12.7 mu M. Moreover, molecular docking analysis suggested that IIc could occupy the colchicine-binding site in a similar way with typical tubulin polymerization inhibitors. These results highlighted the 4-amino-triazolylthioacetone scaffold as potential tubulin polymerization inhibitors for development of highly efficient anticancer agents.

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