Discovery of pyrazole‐carbohydrazide with indole moiety as tubulin polymerization inhibitors and anti‐tumor candidates

作者：Ruo‐Jun Man, Tian Lu, Chi‐Chong Zheng, Tong Li, Meng‐Ke Wu, Dong‐Dong Li, Xuemei He · 发表于：Drug Development Research · 年份：2022 · DOI：10.1002/ddr.22016 · 被引用次数：5 · 研究领域：Synthesis and biological activity、Click Chemistry and Applications、Synthesis and Biological Evaluation

In this work, a series of indole-containing pyrazole-carbohydrazide derivatives A1-A25 were synthesized, and their biological activity on tubulin polymerization inhibition and mitotic catastrophe was evaluated. For introducing indole group to CA-4 pattern, the carbohydrazide linker was used for the first time. As the top hit, A18 suggested notable antiproliferation efficacy and tubulin polymerization inhibitory activity. Inferring comparable antitubulin effect with the positive control Colchicine, A18 indicated obviously lower cyto-toxicity. The cell scratch test showed that A18 could block the cell migration, while the confocal imaging depicted that A18 could induce the mitotic catastrophe via a Colchicine-like approach. The docking simulation visualized the probable binding pattern of A18. With the information in this work, some new hints on modification might be involved in further tubulin-related investigations.