ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PR China.
Arch Pharm (Weinheim). 2011 May;344(5):279-86. doi: 10.1002/ardp.201000069. Epub 2011 Feb 2.
A series of cis-restricted 4,5-diaryl-3-aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA-109, A549, SMMC-7721, and PC-3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G(2)/M phase. The docking research showed the conformation of 5a overlaps well with CA-4 in the crystallized protein complex, suggesting the 4,5-diaryl-3-aminopyrazoles were good mimics of CA-4.
一系列顺式限制的 4,5-二芳基-3-氨基吡唑衍生物被合成，并在体外对五种人癌细胞系（K562、ECA-109、A549、SMMC-7721 和 PC-3）进行了细胞毒性活性测试。化合物 5a、5b、5d 和 6b 对所有测试的细胞系均表现出很强的细胞毒性。对化合物 5a 的初步机制研究表明，它是一种有效的微管蛋白聚合抑制剂，可将细胞周期阻滞在 G2/M 期。对接研究表明，5a 的构象与结晶蛋白复合物中的 CA-4 很好地重叠，这表明 4,5-二芳基-3-氨基吡唑是 CA-4 的良好模拟物。
