Abstract：
As the basic unit of microtubules, tubulin is one of the most important targets in the study of anticarcinogens. A novel series of 3-amino-5-phenylpyrazole derivatives were designed and synthesized, and evaluates for their biological activities. Among them, a majority of compounds exerted excellent inhibitory activities against five cancer cell lines in vitro. Especially, compound 5b showed a strong antiproliferative activity against MCF-7 cells, with IC50 value of 38.37 nM. Further research indicated that compound 5b can inhibit the polymerization of tubulin targeting the tubulin colchicine-binding sites. Furthermore, 5b could arrest MCF-7 cells at the G2/M phase and induce MCF-7 cells apoptotic in a dose-dependent and time-dependent manners, and regulate the level of related proteins expression. Besides, compound 5b could inhibit the cancer cell migration and angiogenesis. In addition, 5b could inhibit tumor growth in MCF-7 xenograft model without obvious toxicity. All these results indicating that 5b could be a promising antitumor agent targeting tubulin colchicine-binding site and it was worth further study.
摘要：
作为微管的基本单位，微管蛋白是抗癌研究中最重要的靶点之一。设计并合成了一系列新的3-氨基-5-苯基吡唑衍生物,并评估其生物活性。其中,大多数化合物在体外对五种癌细胞系具有优异的抑制活性。尤其是,化合物5b对MCF-7细胞具有很强的抗增殖活性，IC50值为38.37nM。进一步的研究表明,化合物5b可以抑制靶向微管蛋白秋水仙碱结合位点的微管蛋白的聚合。此外，5b可以将MCF-7细胞阻滞在G2/M期，并以剂量依赖和时间依赖的方式诱导MCF-7细胞凋亡。并调节相关蛋白的表达水平。此外,化合物5b可抑制癌细胞迁移和血管生成。此外,5b可以抑制MCF-7异种移植模型中的肿瘤生长，无明显毒性。所有这些结果表明5b可能是靶向微管蛋白秋水仙碱结合位点的有希望的抗肿瘤剂，值得进一步研究。
