Refinement and 3D-QSAR Studies of Inhibitors of Cyclophilin A Containing Amide Linker
文献类型：期刊论文
| 作者 | Fan, Feng3,4; Zhu, Jin4; Ni, Shuaishuai4; Cheng, Jiagao3,4; Tang, Yun4; Kang, Congmin1; Li, Jian4; Jiang, Hualiang2,4
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| 刊名 | QSAR & COMBINATORIAL SCIENCE
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| 出版日期 | 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. |
| WOS关键词 | CYTOSOLIC BINDING-PROTEIN ; BIOLOGICAL EVALUATION ; CHEMICAL INHIBITORS ; LIGANDS ; DESIGN ; IMMUNOPHILINS ; SANGLIFEHRIN ; CORONAVIRUS ; COMPLEXES ; BIOASSAY |
| 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研究方向 | Pharmacology & Pharmacy ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000263587800004 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 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. |
入库方式： OAI收割
来源：上海药物研究所
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