Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues

doi:10.1016/S0968-0896(02)00161-X

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues
	Cheng, F ; Shen, JH; Luo, XM; Zhu, WL; Gu, JD; Ji, RY ; Jiang, HL; Chen, KX
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2002-09
卷号	10 期号:9 页码:2883-2891
ISSN号	0968-0896
DOI	10.1016/S0968-0896(02)00161-X
文献子类	Article
英文摘要	Artemisinin (Qinghaosu) is a natural constituent found in Artemisia annua L, which is an effective drug against chloroquine-resistant Plasmodium falciparum strains and cerebral malaria, The antimalarial activities of arternisinin and its analogues appear to be mediated by the interactions of the drugs with hemin. In order to understand the antimalarial mechanism and the relationship between the physicochemical properties and the antimalarial activities of artemisinin analogues, we performed molecular docking simulations to probe the interactions of these analogues with hemin, and then performed three-dimensional quantitative structure-activity relationship (3-D-QSAR) studies on the basis of the docking models employing comparative molecular force fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Molecular docking simulations generated probable 'bioactive' conformations of artemisinin analogues and provided a new insight into the antimalarial mechanism. The subsequent partial least squares (PLS) analysis indicates that the calculate binding energies correlate well with the experimental activity values. The CoMFA and CoMSIA models based on the bioactive conformations proved to have good predictive ability and in turn match well with the docking result, which further testified the reliability of the docking model. Combining these results, that is molecular docking and 3-D-QSAR, together, the binding model and activity of new synthesized artemisinin derivatives were well explained. (C) 2002 Elsevier Science Ltd. All rights reserved.
WOS关键词	DERIVATIVES ; QINGHAOSU
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000177484800007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274332]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Shen, JH
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Drug Discovery & Design, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Cheng, F,Shen, JH,Luo, XM,et al. Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2002,10(9):2883-2891.
APA	Cheng, F.,Shen, JH.,Luo, XM.,Zhu, WL.,Gu, JD.,...&Chen, KX.(2002).Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues.BIOORGANIC & MEDICINAL CHEMISTRY,10(9),2883-2891.
MLA	Cheng, F,et al."Molecular docking and 3-D-QSAR studies on the possible antimalarial mechanism of artemisinin analogues".BIOORGANIC & MEDICINAL CHEMISTRY 10.9(2002):2883-2891.