Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
Department of Pharmacy, Characteristic Medical Center of PAP, Tianjin, China.
J Biomol Struct Dyn. 2021 Apr;39(6):2176-2188. doi: 10.1080/07391102.2020.1745284. Epub 2020 Mar 31.
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 , , and possessed high inhibition activity against A-549 cell lines with IC values at 4.91, 3.22, 27.43 and 18.14 μM, respectively, better than that of 5-fluorouracil (IC=59.27 μM). and also exhibited significant inhibitory activity towards HCT-8 and Bel7402 cell lines. Interestingly, the Heat Shock Protein 90α (Hsp90α, PDB ID: 1UYK) was found to be the potential drug target of these synthesized compounds with the aid of PharmMapper server (http://lilab.ecust.edu.cn/pharmmapper/) and docking module of Schrödinger (Maestro 10.2). Additionally, molecular dynamics simulation was performed out to explore the most likely binding mode of compound with Hsp90α.Communicated by Ramaswamy H. Sarma.
合成了一系列新型含吡唑的酰亚胺衍生物，并对它们在 A-549、Bel7402 和 HCT-8 细胞系中的抗癌活性进行了评估。在这些化合物中，化合物 、 和 对 A-549 细胞系具有高抑制活性，IC 值分别为 4.91、3.22、27.43 和 18.14 μM，优于 5-氟尿嘧啶（IC=59.27 μM）。化合物 和 对 HCT-8 和 Bel7402 细胞系也表现出显著的抑制活性。有趣的是，借助 PharmMapper 服务器（http://lilab.ecust.edu.cn/pharmmapper/）和 Schrödinger 的对接模块（Maestro 10.2），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标。此外，还进行了分子动力学模拟，以探索化合物 与 Hsp90α 的最可能结合模式。通讯作者为 Ramaswamy H. Sarma。
