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

doi:10.1016/j.ejmech.2007.06.021

CORC > 昆明植物研究所 > 中国科学院昆明植物研究所 > 植物化学与西部植物资源持续利用国家重点实验室

	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
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2008-05-01
卷号	43 期号:5 页码:925-938
关键词	3d-qsar Gold Comfa Comsia Checkpoint Kinase Weel
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2007.06.021
文献子类	Article
英文摘要	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.
学科主题	Chemistry ; Medicinal
WOS关键词	TYROSINE KINASE ; BINDING-AFFINITY ; FLEXIBLE DOCKING ; CELL-DIVISION ; CYCLE ; VALIDATION ; FIELD ; CHK1
WOS研究方向	Pharmacology & Pharmacy
语种	英语
WOS记录号	WOS:000256570800004
公开日期	2011-11-24
内容类型	期刊论文
源URL	[http://ir.kib.ac.cn:8080/handle/151853/1875]
专题	昆明植物研究所_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.