3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1

doi:10.1016/j.ejmech.2007.04.020

	3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1
	Yi, Ping 1,2; Qiu, Minghua1
	2008-03-01
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	43 期号:3 页码:604-613
摘要	In order to better understand the structural and chemical features of c-Jun N-terminal kinase-1 (JNK-1), which is a member of the mitogen activated protein kinase (MAP kinase) family of enzymes responsible for the serine/threonine phosphorylation of intracellular targets, 3D-QSAR studies of some aminopyridine carboxamides as c-Jun N-terminal kinase inhibitors were performed by comparative molecular field analysis (CoMFA) to rationalize the structural requirements responsible for the inhibitory activity of these compounds. The genetic algorithm of GOLD3.1 has been employed to position 54 aminopyridine carboxamides in the active sites of JNK-1 to determine the probable binding conformation. The docking results provided a reliable conformational alignment scheme for 3D-QSAR model. Based on the docking conformations, highly predictive comparative molecular field analysis (CoMFA) was performed with a cross-validated q(2) of 0.585. The non-cross-validated analysis with six optimum components revealed a conventional r(2) value of 0.988, F = 5 10.200, and an estimated standard error of 0.071. Furthermore, the CoMFA model was mapped back to the binding sites of JNK-1, to get a better understanding of vital interactions between the aminopyridine carboxamides and the kinase. Based on the docking and CoMFA analyses, we have identified some key features in the aminopyridine carboxamides that are responsible for JNK-1 inhibitory activity. The analyses may be used to design more potent aminopyridine carboxamides and predict their activity prior to synthesis. (c) 2007 Elsevier Masson SAS. All rights reserved.
关键词	3d-qsar Gold Comfa C-jun N-terminal Kinase-1
学科领域	Chemistry ; Medicinal
DOI	10.1016/j.ejmech.2007.04.020
收录类别	SCI
语种	英语
WOS记录号	WOS:000254777400017
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/1897
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, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Yunnan, 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,Qiu, Minghua. 3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2008,43(3):604-613.
APA	Yi, Ping,&Qiu, Minghua.(2008).3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,43(3),604-613.
MLA	Yi, Ping,et al."3D-QSAR and docking studies of aminopyridine carboxamide inhibitors of c-Jun N-terminal kinase-1".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 43.3(2008):604-613.

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