%0 Journal Article
%T Combined Pharmacophore Modeling, Docking, and 3D-QSAR Studies of PLK1 Inhibitors
%A Shuai Lu
%A Hai-Chun Liu
%A Ya-Dong Chen
%A Hao-Liang Yuan
%A Shan-Liang Sun
%A Yi-Ping Gao
%A Pei Yang
%A Liang Zhang
%A Tao Lu
%J International Journal of Molecular Sciences
%D 2011
%I MDPI AG
%R 10.3390/ijms12128713
%X 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-1 H-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 q 2 and r 2 pred 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.
%K PLK1
%K 3D-QSAR
%K pharmacophore
%K molecular docking
%U http://www.mdpi.com/1422-0067/12/12/8713