Synthesis, evaluation, molecular dynamics simulation and targets identification of novel pyrazole-containing imide derivatives
Synthesis, evaluation, molecular dynamics simulation and targets identification of novel pyrazole-containing imide derivatives
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新型吡唑酰亚胺衍生物的合成、评价、分子动力学模拟及靶标鉴定
DOI：
10.1080/07391102.2020.1745284
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发表时间：
2020-03-30
影响因子：
4.4
通讯作者：
Dong, Weili
中科院分区：
文献类型：
--
作者：
Cai, Wenxi;Wu, Jingwei;Dong, Weili
合成了一系列新的新型吡唑酰亚胺衍生物，并评估了它们对 A-549、Bel7402 和 HCT-8 细胞系的抗癌活性。其中化合物A2、A4、A11和A14对A-549细胞系具有较高的抑制活性，IC50值分别为4.91、3.22、27.43和18.14μM，优于5-氟尿嘧啶(IC50=59.27μM)。 A2、A4 和 A11 对 HCT-8 和 Bel7402 细胞系也表现出显着的抑制活性。有趣的是，借助PharmMapper服务器（）和Schrodinger（Maestro 10.2）的对接模块，发现热休克蛋白90α（Hsp90α，PDB ID：1UYK）是这些合成化合物的潜在药物靶点。此外，还进行了分子动力学模拟，以探索化合物A2与Hsp90α最可能的结合模式。拉马斯瓦米·萨尔马 (Ramaswamy H. Sarma) 通讯
A new series of novel pyrazole-containing imide derivatives were synthesized and evaluated for their anticancer activities against A-549, Bel7402, and HCT-8 cell lines. Among these compounds A2, A4, A11 and A14 possessed high inhibition activity against A-549 cell lines with IC50 values at 4.91, 3.22, 27.43 and 18.14 mu M, respectively, better than that of 5-fluorouracil (IC50=59.27 mu M). A2, A4, and A11 also exhibited significant inhibitory activity towards HCT-8 and Bel7402 cell lines. Interestingly, the Heat Shock Protein 90 alpha (Hsp90 alpha, PDB ID: 1UYK) was found to be the potential drug target of these synthesized compounds with the aid of PharmMapper server () and docking module of Schrodinger (Maestro 10.2). Additionally, molecular dynamics simulation was performed out to explore the most likely binding mode of compound A2 with Hsp90 alpha. Communicated by Ramaswamy H. Sarma