设计并合成了一系列新的1H-吡咯并[3,2-c]吡啶衍生物作为秋水仙碱结合位点抑制剂。初步生物学评估表明，大多数目标化合物在体外对三种癌细胞系（HeLa、SGC-7901 和 MCF-7）表现出中等至优异的抗肿瘤活性。其中，10t对三种癌细胞系表现出最有效的活性，IC50值范围为0.12至0.21μM。微管蛋白聚合实验表明，10t 在 3μM 和 5μM 浓度下有效抑制微管蛋白聚合，免疫染色测定表明，10t 在 0.12μM 浓度下显着破坏微管蛋白微管动力学。此外，细胞周期研究和细胞凋亡分析表明，0.12μM、0.24μM和0.36μM浓度的10t显着引起G2/M期细胞周期停滞和凋亡。分子模型研究结果表明，10t 通过与秋水仙碱位点 Thrα179 和 Asnβ349 形成氢键与微管蛋白相互作用。此外，理化性质的预测表明10t很好地符合Lipinski的五法则。

A new series of 1H-pyrrolo[3,2-c]pyridine derivatives were designed and synthesised as colchicine-binding site inhibitors. Preliminary biological evaluations showed that most of the target compounds displayed moderate to excellent antitumor activities against three cancer cell lines (HeLa, SGC-7901, and MCF-7) in vitro. Among them, 10t exhibited the most potent activities against three cancer cell lines with IC50 values ranging from 0.12 to 0.21 μM. Tubulin polymerisation experiments indicated that 10t potently inhibited tubulin polymerisation at concentrations of 3 μM and 5 μM, and immunostaining assays revealed that 10t remarkably disrupted tubulin microtubule dynamics at a concentration of 0.12 μM. Furthermore, cell cycle studies and cell apoptosis analyses demonstrated that 10t at concentrations of 0.12 μM, 0.24 μM, and 0.36 μM significantly caused G2/M phase cell cycle arrest and apoptosis. The results of molecular modelling studies suggested that 10t interacts with tubulin by forming hydrogen bonds with colchicine sites Thrα179 and Asnβ349. In addition, the prediction of physicochemical properties disclosed that 10t conformed well to the Lipinski's rule of five.