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Int. J. Mol. Sci. 2010, 11(10), 3705-3724; doi:10.3390/ijms11103705
Article

Molecular Modeling Studies of 4,5-Dihydro-1H-pyrazolo[4,3-h] quinazoline Derivatives as Potent CDK2/Cyclin A Inhibitors Using 3D-QSAR and Docking

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Received: 19 July 2010 / Revised: 3 September 2010 / Accepted: 20 September 2010 / Published: 28 September 2010
(This article belongs to the Special Issue Recent Advances in QSAR/QSPR Theory)

Abstract

CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r2cv values of 0.747 and 0.518 and r2 values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.
Keywords: CDK2/cyclin A; 3D-QSAR; CoMFA; CoMSIA; docking CDK2/cyclin A; 3D-QSAR; CoMFA; CoMSIA; docking
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Ai, Y.; Wang, S.-T.; Sun, P.-H.; Song, F.-J. Molecular Modeling Studies of 4,5-Dihydro-1H-pyrazolo[4,3-h] quinazoline Derivatives as Potent CDK2/Cyclin A Inhibitors Using 3D-QSAR and Docking. Int. J. Mol. Sci. 2010, 11, 3705-3724.

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