Discovering Novel alpha-aminoacyl-Containing Proline Derivatives with Potent and Selective Inhibitory Activity Against Dipeptidyl Peptidase IV: Design, Synthesis, Biological Evaluation, and Molecular Modeling
文献类型：期刊论文
| 作者 | Zhang, Xiaodong1; Wang, Jiang1 ; Su, Mingbo2; Li, Zeng1; Li, Jingya2; Li, Jia2; Liu, Hong1
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| 刊名 | CHEMICAL BIOLOGY & DRUG DESIGN
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| 出版日期 | 2012-12 |
| 卷号 | 80期号:6页码:843-852 |
| 关键词 | a-aminoacyl-containing proline derivatives dipeptidyl peptidase IV inhibitor molecular docking type 2 diabetes |
| ISSN号 | 1747-0277 |
| DOI | 10.1111/j.1747-0285.2012.01438.x |
| 文献子类 | Article |
| 英文摘要 | On the basis of the enzyme-binding features of known potent inhibitors of dipeptidyl peptidase IV, novel alpha-aminoacyl-containing proline analogs (8Aa8Ak, 8Ba8Bj, 8Ca8Ck, and 8Da8Di) with the S configuration were designed, synthesized, and their activity profiled. Their structural features were determined by nuclear magnetic resonance (NMR) spectroscopy, low- and high-resolution mass spectroscopy. Five compounds (8Aa, 8Aj, 8Ch, 8Ck, and 8Dc) were shown to have promising inhibitory activities against dipeptidyl peptidase IV. Two of them, compounds 8Aa and 8Aj inhibited dipeptidyl peptidase IV with IC50 values of 4.56 and 8.4 mu m, respectively, and displayed no inhibition at other dipeptidyl peptidase IV. The possible binding modes of compounds 6, 7, 8Aa, and 8Aj with dipeptidyl peptidase IV were also explored by molecular docking simulation. This study provides promising new templates for the further development of antidiabetic agents. |
| WOS关键词 | CRYSTAL-STRUCTURE ; INSULIN SENSITIVITY ; DPP-4 INHIBITOR ; HIGHLY POTENT ; VILDAGLIPTIN ; REVEALS ; COMPLEX |
| 资助项目 | National Basic Research Program of China[2009CB940903] ; National Basic Research Program of China[2009CB918502] ; National Natural Science Foundation of China[20721003] ; National Natural Science Foundation of China[81025017] ; National S&T Major Projects[2012ZX09103-101-072] ; Silver Project[260644] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000310469500005 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277870]  |
| 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 |
| 通讯作者 | Liu, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201303, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xiaodong,Wang, Jiang,Su, Mingbo,et al. Discovering Novel alpha-aminoacyl-Containing Proline Derivatives with Potent and Selective Inhibitory Activity Against Dipeptidyl Peptidase IV: Design, Synthesis, Biological Evaluation, and Molecular Modeling[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2012,80(6):843-852. |
| APA | Zhang, Xiaodong.,Wang, Jiang.,Su, Mingbo.,Li, Zeng.,Li, Jingya.,...&Liu, Hong.(2012).Discovering Novel alpha-aminoacyl-Containing Proline Derivatives with Potent and Selective Inhibitory Activity Against Dipeptidyl Peptidase IV: Design, Synthesis, Biological Evaluation, and Molecular Modeling.CHEMICAL BIOLOGY & DRUG DESIGN,80(6),843-852. |
| MLA | Zhang, Xiaodong,et al."Discovering Novel alpha-aminoacyl-Containing Proline Derivatives with Potent and Selective Inhibitory Activity Against Dipeptidyl Peptidase IV: Design, Synthesis, Biological Evaluation, and Molecular Modeling".CHEMICAL BIOLOGY & DRUG DESIGN 80.6(2012):843-852. |
入库方式： OAI收割
来源：上海药物研究所
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