Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker

doi:10.1002/qsar.200860076

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	Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker
	Fan, Feng 3,4; Zhu, Jin 4; Ni, Shuaishuai 4; Cheng, Jiagao 3,4; Tang, Yun 4; Kang, Congmin 1; Li, Jian 4; Jiang, Hualiang2,4
刊名	QSAR & COMBINATORIAL SCIENCE
	2009-02
卷号	28 期号:2 页码:183-193
关键词	Amide linker 3D-QSAR CoMFA CoMSIA CypA
ISSN号	1611-020X
DOI	10.1002/qsar.200860076
文献子类	Article
英文摘要	Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing essential role in many biological processes, and the discovery of CypA inhibitor is now of special interest in the treatment of immunological disorders. In this work, molecular modeling studies were performed to develop a predictive Common Pharmacophore Hypothesis (CPH) and use it for alignment in 3D-QSAR studies using CoMFA and CoMSIA. A total of 30 compounds containing an amide fragment as the key linker, consisting of 17 of our previously discovered CypA inhibitors and 13 other inhibitors reported in the literature, were selected for pharmacophore refinement and 3D-QSAR studies. The best pharmacophore hypothesis AADR, which had two hydrogen bond acceptors, a hydrogen bond donor, and an aromatic ring, was obtained and used for the alignment of molecules in CoMFA and CoMSIA model development. The models showed a good r(2) value of 0.992 and 0.949 for CoMFA and CoMSIA, respectively. The contour maps of the models were analyzed to give structural insight for activity improvement of future novel CypA inhibitors. The CPH can also provide a powerful template for virtual screening and design of new CypA inhibitors.
资助项目	863 Hi-Tech Program of China[2006AA020404] ; Shanghai Ministry of Science and Technology[07QA14013] ; National Natural Science Foundation of China[20802018] ; National Natural Science Foundation of China[20772070] ; Natural Science Foundation of Shanghai[08ZR1406500]
WOS关键词	CYTOSOLIC BINDING-PROTEIN ; BIOLOGICAL EVALUATION ; CHEMICAL INHIBITORS ; LIGANDS ; DESIGN ; IMMUNOPHILINS ; SANGLIFEHRIN ; CORONAVIRUS ; COMPLEXES ; BIOASSAY
WOS研究方向	Pharmacology & Pharmacy ; Chemistry ; Computer Science
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000263587800004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279338]
专题	药物发现与设计中心
通讯作者	Fan, Feng
作者单位	1.Qingdao Univ Sci & Technol, Coll Chem Engn, Qingdao 260042, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China; 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;
推荐引用方式 GB/T 7714	Fan, Feng,Zhu, Jin,Ni, Shuaishuai,et al. Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker[J]. QSAR & COMBINATORIAL SCIENCE,2009,28(2):183-193.
APA	Fan, Feng.,Zhu, Jin.,Ni, Shuaishuai.,Cheng, Jiagao.,Tang, Yun.,...&Jiang, Hualiang.(2009).Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker.QSAR & COMBINATORIAL SCIENCE,28(2),183-193.
MLA	Fan, Feng,et al."Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker".QSAR & COMBINATORIAL SCIENCE 28.2(2009):183-193.