3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA

doi:10.1016/j.ejmech.2007.06.021

	3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA
	Yi, Ping 1,2; Fang, Xin 1,2; Qiu, Minghua1
	2008-05-01
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	43 期号:5 页码:925-938
摘要	Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on 97 4-phenylpyrrolo[3,4-c]-carbazole-1,3(2H,6H)-dione inhibitors, based on molecular docking scores obtained by using GOLD 3.1, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices (CoMSIA). The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. Based on the docking conformations and alignments, highly predictive CoMFA and CoMSIA were obtained with cross-validated q(2) value of 0.828 and 0.796, respectively, and non-cross-validated partial least-squares (PLS) analysis with the optimum components of five showed a conventional r(2) of 0.962 and 0.949, respectively. The predictive ability was validated by compounds that were not included in the training set. Furthermore, the CoMFA and CoMSIA model plots were mapped back to the binding sites of Checkpoint Kinase Weel, to get a better understanding of vital interactions between the inhibitors and Weel kinase. As a result, we have identified some key features in the 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones responsible for the Weel inhibitory activity that may be used to design more potent 4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones and predict their activity prior to synthesis. (C) 2007 Elsevier Masson SAS. All rights reserved.
关键词	3d-qsar Gold Comfa Comsia Checkpoint Kinase Weel
学科领域	Chemistry ; Medicinal
DOI	10.1016/j.ejmech.2007.06.021
收录类别	SCI
语种	英语
WOS记录号	WOS:000256570800004
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/1875
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources W China, Kunming Inst Bot, Kunming 650204, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China
推荐引用方式 GB/T 7714	Yi, Ping,Fang, Xin,Qiu, Minghua. 3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2008,43(5):925-938.
APA	Yi, Ping,Fang, Xin,&Qiu, Minghua.(2008).3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,43(5),925-938.
MLA	Yi, Ping,et al."3D-QSAR studies of Checkpoint Kinase Weel inhibitors based on molecular docking, CoMFA and CoMSIA".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 43.5(2008):925-938.

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