Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors.
Combined pharmacophore modeling, docking, and 3D-QSAR studies of PLK1 inhibitors.
复制标题
PLK1 抑制剂的组合药效团建模、对接和 3D-QSAR 研究
DOI：
10.3390/ijms12128713
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发表时间：
2011
影响因子：
5.6
通讯作者：
Lu T
中科院分区：
文献类型：
--
作者：
Lu S;Liu HC;Chen YD;Yuan HL;Sun SL;Gao YP;Yang P;Zhang L;Lu T
Polo样激酶1是细胞有丝分裂过程中具有多种生物学作用的重要酶，是开发新型抗肿瘤药物的一个很有前途的靶点。采用分子对接、药效团建模和三维定量构效关系（3D-QSAR）相结合的方法，对一系列4，5-二氢-1H-吡唑并[4，3-h]喹唑啉类PLK 1抑制剂进行了研究。采用常见的亚结构、分子对接和基于药效团的比对方法建立了不同的3D-QSAR模型。比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）模型给出了统计学显著的结果。这些模型显示出良好的q2和r2 pred值，并显示出对测试集验证的良好响应。从3D-QSAR等高线图获得的所有结构见解与PLK 1的可用晶体结构一致。三维定量构效关系模型结合药效团模型得到的等值线图有助于更好地解释构效关系。这些令人满意的结果可能有助于设计新的PLK 1抑制剂。这是首次报道PLK 1抑制剂的3D-QSAR研究。
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 r2 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.
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DOI：
10.1073/pnas.0701140104
发表时间：
2007-03-13
影响因子：
11.1
作者：
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