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

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

1
Laboratory for Natural Product Chemistry, College of Pharmacy, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China
2
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
3
College of Life Science/Key Laboratory for Biotechnology of the State Ethnic Affairs Commission, South Central University for Nationalities, 708 Minyuan Road, Wuhan 430074, China
*
Authors to whom correspondence should be addressed.
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 (CC BY 3.0).

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MDPI and ACS Style

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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