Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f, 8j, and 8o manifested more potent antiproliferative activities against HeLa cell line with IC₅₀ values of 0.04, 0.05 and 0.16 μM, respectively, representing 100-, 82-, and 25-fold improvements of the activity compared to compound 6. Furthermore, the representative compound, 8j, was found to induce significant cell cycle arrest at the G₂/M phase in HeLa cell lines via a concentration-dependent manner. Meanwhile, compound 8b exhibited the most potent tubulin polymerization inhibitory activity with an IC₅₀ value of 5.9 μM, which was almost as active as that of CA-4 (IC₅₀ = 4.2 μM). Additionally, molecular docking analysis suggested that 8b formed stable interactions in the colchicine-binding site of tubulin.

根据我们以前的研究，合成了三个具有3,4,5-三甲氧基苯基部分的新的三唑基硫代乙酰胺系列，并评估了其抗增殖活性和对微管蛋白聚合的抑制作用。与我们的先导化合物6相比，最有希望的化合物8b和8j对MCF-7，HeLa和HT-29细胞系表现出更重要的抗增殖活性。此外，类似物8f，8j和8o表现出对HeLa细胞系更有效的抗增殖活性，IC ₅₀值分别为0.04、0.05和0.16μM，与化合物相比，活性提高了100倍，82倍和25倍6。此外，发现代表性化合物8j通过浓度依赖的方式在HeLa细胞系的G ₂ / M期诱导明显的细胞周期停滞。同时，化合物8b表现出最有效的微管蛋白聚合抑制活性，IC ₅₀值为5.9μM，几乎与CA-4的活性相同（IC ₅₀  = 4.2μM）。另外，分子对接分析表明8b在微管蛋白的秋水仙碱结合位点形成稳定的相互作用。