1. Synthesis, evaluation, molecular dynamics simulation and targets identification of novel pyrazole-containing imide derivatives.
- Author
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Cai W, Wu J, Sun Y, Liu A, Wang R, Ma Y, Shuqing Wang, and Dong W
- Subjects
- Cell Line, Tumor, Cell Proliferation, Drug Screening Assays, Antitumor, Imides pharmacology, Molecular Docking Simulation, Molecular Structure, Pyrazoles pharmacology, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Molecular Dynamics Simulation
- Abstract
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 IC
50 values at 4.91, 3.22, 27.43 and 18.14 μM, respectively, better than that of 5-fluorouracil (IC50 =59.27 μM). A2, A4, and A11 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 A2 with Hsp90α.Communicated by Ramaswamy H. Sarma.- Published
- 2021
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