School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, People's Republic of China.
Bioorg Med Chem. 2012 Aug 15;20(16):4895-900. doi: 10.1016/j.bmc.2012.06.056. Epub 2012 Jul 10.
A series of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives (5a-8d) have been designed and synthesized, and their biological activities were also evaluated as potential antitumor and cyclin dependent kinase 2 (CDK2) inhibitors. Among all the compounds, compound 5a displayed the most potent CDK2/cyclin E inhibitory activity in vitro, with an IC(50) of 0.98 ± 0.06 μM. Antitumor assays indicated that compound 5a owned high antiproliferative activity against MCF-7 and B16-F10 cancer cell lines with IC(50) values of 1.88 ± 0.11 and 2.12 ± 0.15 μM, respectively. Docking simulation was performed to insert compound 5a into the crystal structure of CDK2 at active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity in tumor growth may be a potential anticancer agent.
设计并合成了一系列 N-((1,3-二苯基-1H-吡唑-4-基)甲基)苯胺衍生物（5a-8d），并评估了它们作为潜在抗肿瘤和细胞周期蛋白依赖性激酶 2 (CDK2)抑制剂的生物活性。在所有化合物中，化合物 5a 在体外显示出最强的 CDK2/细胞周期蛋白 E 抑制活性，IC50 为 0.98 ± 0.06 μM。抗肿瘤测定表明，化合物 5a 对 MCF-7 和 B16-F10 癌细胞系具有高的增殖抑制活性，IC50 值分别为 1.88 ± 0.11 和 2.12 ± 0.15 μM。进行了对接模拟，将化合物 5a 插入 CDK2 活性部位的晶体结构中，以确定可能的结合模型。基于初步结果，具有肿瘤生长抑制活性的化合物 5a 可能是一种有潜力的抗癌药物。
