A series of indole-based [1,2,4]triazolo [4,3-a]pyridine derivatives was designed and synthesized as novel microtubulin polymerization inhibitors by using a conformational restriction strategy. These compounds exhibited moderate to potent anti-proliferative activities against a panel of cancer cell lines (HeLa, A549, MCF-7 and HCT116). Among them, compound 12d featuring a N-methyl-5-indolyl substituent at the C-6 position of the [1,2,4]triazolo [4,3-a]pyridine core exhibited the highest antiproliferative activity with the IC₅₀ values ranging from 15 to 69 nM, and remarkable inhibitory effect on tubulin polymerization with an IC₅₀ value of 1.64 μM. Mechanistic studies revealed that compound 12d induced cellular apoptosis and cell cycle arrest at the G₂/M phase in a dose-dependent fashion. Moreover, compound 12d significantly suppressed wound closure and disturbed microtubule networks.

通过使用构象限制策略，设计并合成了一系列基于吲哚的 [1,2,4] 三唑并 [4,3- a ] 吡啶衍生物作为新型微管蛋白聚合抑制剂。这些化合物对一组癌细胞系（HeLa、A549、MCF-7 和 HCT116）表现出中等至强效的抗增殖活性。其中，在[1,2,4]三唑并[4,3- a ]吡啶核心的C- 6位具有N-甲基-5-吲哚基取代基的化合物12d表现出最高的抗增殖活性，IC ₅₀值范围从 15 到 69 nM，对微管蛋白聚合有显着的抑制作用，IC ₅₀值为 1.64 μM。机理研究表明，化合物12d以剂量依赖性方式在G ₂ /M 期诱导细胞凋亡和细胞周期停滞。此外，化合物12d显着抑制伤口闭合并扰乱微管网络。