Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay
文献类型：期刊论文
| 作者 | Li, J ; Chen, J; Gui, CS; Zhang, L; Qin, Y; Xu, Q; Zhang, J; Liu, H; Shen, X; Jiang, HL
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2006-04-01 |
| 卷号 | 14期号:7页码:2209-2224 |
| 关键词 | cyclophilin A inhibitor drug design virtual screening |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2005.11.006 |
| 文献子类 | Article |
| 英文摘要 | Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS-1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micromolar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-I), and four of which (compounds 16b, 16h 16k,. and 18g) showed high CypA PPIase inhibition activities with IC50S of 2.5-6,2 mu M. Pharmacological assay indicated that these four Compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells. (c) 2005 Elsevier Ltd. All rights reserved. |
| WOS关键词 | CYTOSOLIC BINDING-PROTEIN ; MOLECULAR DOCKING ; CYCLOSPORINE-A ; CALCINEURIN ; CELLS ; FK506 ; ASSAY ; IMMUNOPHILINS ; ISOMERASES ; STRATEGIES |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000236015000010 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273622]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 药理学第三研究室 |
| 通讯作者 | Liu, H |
| 作者单位 | 1.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med,Grad Sch,Shanghai Inst Biol, Shanghai 201203, Peoples R China 2.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China 3.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, J,Chen, J,Gui, CS,et al. Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2006,14(7):2209-2224. |
| APA | Li, J.,Chen, J.,Gui, CS.,Zhang, L.,Qin, Y.,...&Jiang, HL.(2006).Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay.BIOORGANIC & MEDICINAL CHEMISTRY,14(7),2209-2224. |
| MLA | Li, J,et al."Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay".BIOORGANIC & MEDICINAL CHEMISTRY 14.7(2006):2209-2224. |
入库方式： OAI收割
来源：上海药物研究所
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