Int. J. Mol. Sci. 2011, 12(12), 8713-8739; doi:10.3390/ijms12128713
Article

Combined Pharmacophore Modeling, Docking, and 3D-QSAR Studies of PLK1 Inhibitors

Shuai Lu 1,2 email, Hai-Chun Liu 1 email, Ya-Dong Chen 1,* email, Hao-Liang Yuan 1 email, Shan-Liang Sun 2 email, Yi-Ping Gao 2 , Pei Yang 3 email, Liang Zhang 2 email and Tao Lu 2,4,* email
1 Laboratory of Molecular Design and Drug Discovery, China Pharmaceutical University, Nanjing 211169, China 2 Department of Organic Chemistry, China Pharmaceutical University, Nanjing 211169, China 3 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211169, China 4 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211169, China
* Authors to whom correspondence should be addressed.
Received: 4 September 2011; in revised form: 1 November 2011 / Accepted: 21 November 2011 / Published: 1 December 2011
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Abstract: Polo-like kinase 1, an important enzyme with diverse biological actions in cell mitosis, is a promising target for developing novel anticancer drugs. A combined molecular docking, structure-based pharmacophore modeling and three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed on a set of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as PLK1 inhibitors. The common substructure, molecular docking and pharmacophore-based alignment were used to develop different 3D-QSAR models. The comparative molecular field analysis (CoMFA) and comparative molecule similarity indices analysis (CoMSIA) models gave statistically significant results. These models showed good q2 and r2pred values and revealed a good response to test set validation. All of the structural insights obtained from the 3D-QSAR contour maps are consistent with the available crystal structure of PLK1. The contour maps obtained from the 3D-QSAR models in combination with the structure based pharmacophore model help to better interpret the structure-activity relationship. These satisfactory results may aid the design of novel PLK1 inhibitors. This is the first report on 3D-QSAR study of PLK1 inhibitors.
Keywords: PLK1; 3D-QSAR; pharmacophore; molecular docking

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Cite This Article

MDPI and ACS Style

Lu, S.; Liu, H.-C.; Chen, Y.-D.; Yuan, H.-L.; Sun, S.-L.; Gao, Y.-P.; Yang, P.; Zhang, L.; Lu, T. Combined Pharmacophore Modeling, Docking, and 3D-QSAR Studies of PLK1 Inhibitors. Int. J. Mol. Sci. 2011, 12, 8713-8739.

AMA Style

Lu S, Liu H-C, Chen Y-D, Yuan H-L, Sun S-L, Gao Y-P, Yang P, Zhang L, Lu T. Combined Pharmacophore Modeling, Docking, and 3D-QSAR Studies of PLK1 Inhibitors. International Journal of Molecular Sciences. 2011; 12(12):8713-8739.

Chicago/Turabian Style

Lu, Shuai; Liu, Hai-Chun; Chen, Ya-Dong; Yuan, Hao-Liang; Sun, Shan-Liang; Gao, Yi-Ping; Yang, Pei; Zhang, Liang; Lu, Tao. 2011. "Combined Pharmacophore Modeling, Docking, and 3D-QSAR Studies of PLK1 Inhibitors." Int. J. Mol. Sci. 12, no. 12: 8713-8739.

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