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Acta Phys. -Chim. Sin.  2009, Vol. 25 Issue (05): 890-896    DOI: 10.3866/PKU.WHXB20090409
Molecular Docking and 3D-QSAR on Maleimide Derivatives as Glycogen Synthase Kinase-3β Inhibitors
WEI Zhuo, ZHANG Huai, CUI Wei, JI Ming-Juan
College of Chemistry and Chemical Engineering, Graduate University of the Chinese Academy of Sciences, Beijing 100049, P. R. China; Laboratory of Computational Geodynamics, Graduate University of the Chinese Academy of Sciences, Beijing 100049, P. R. China
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Molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) approaches were used to characterize the binding features of two different series of maleimide glycogen synthase kinase-3β(GSK-3β) inhibitors, 3-(indol-3-yl)-4-(1H-indazol-3-yl) maleimides and 3-(benzofuran-3-yl)-4-(indol-3-yl) maleimides. First, molecular docking was applied to characterize the binding modes and interactions between ligands and GSK-3β. A comparative molecular field analysis (CoMFA) and comparative molecular similarity indice analysis (CoMSIA) were then employed to develop 3D-QSAR models of 48 compounds. The excellent predictive capability of these 3D-QSAR models were validated by a satisfactory correlation coefficient using leave-one-out cross-validation q2 values (q2 values were 0.669 and 0.683 for CoMFA and CoMSIA, respectively). Satisfactory predictions on externally tested compounds also validated the models. Using the 3D-QSAR models, 9 molecules were designed with predicted good binding affinities in terms of molecular docking score and they also had good predicted values for inhibition.

Key wordsGSK-3β      3D-QSAR      CoMFA      CoMSIA      Molecular docking     
Received: 20 October 2008      Published: 16 February 2009
MSC2000:  O641  
Corresponding Authors: JI Ming-Juan     E-mail:
Cite this article:

WEI Zhuo, ZHANG Huai, CUI Wei, JI Ming-Juan. Molecular Docking and 3D-QSAR on Maleimide Derivatives as Glycogen Synthase Kinase-3β Inhibitors. Acta Phys. -Chim. Sin., 2009, 25(05): 890-896.

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