Synthesis, evaluation, molecular dynamics simulation and targets identification of novel pyrazole-containing imide derivatives.

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.