Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action
文献类型：期刊论文
| 作者 | Wu, Jiahui2; Li, Yi1; Chen, Kaixian3 ; Jiang, Hualiang3; Xu, Ming-Hua1; Liu, Dongxiang2
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2013-02 |
| 卷号 | 60页码:441-450 |
| 关键词 | Benzofuran-3-yl(phenyl)methanones Binding mode Deacetylation Inhibitor SIRT1 |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2012.12.026 |
| 文献子类 | Article |
| 英文摘要 | SIRT1 is a NAD(+)-dependent deacetylase. Here we described new SIRT1 inhibitors with the scaffold of benzofuran-3-yl(phenyl)methanone. The inhibitors were predicted to bind in C-pocket of SIRT1, forming hydrophobic interactions with Phe273, Phe312 and Ile347. Introducing hydroxyl to meta position of phenyl may form H-bond with Asn346. Indeed, (2,5-dihydroxyphenyl)(5-hydroxy-1-benzofuran-3-yl) methanone (16), an analogue with hydroxyls at ortho and meta positions, showed greater inhibition. The binding mode was validated by structural modifications and kinetic studies. Since C-pocket is the site where the nicotinamide moiety of NAD(+) binds and the hydrolysis takes place, binding of 16 in C-pocket would block the transformation of NAD(+) to productive conformation and hence inhibit the deacetylase activity. Consistently, 16 inhibited SIRT1 through up-regulating p53 acetylation on cellular level. (C) 2012 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | SMALL-MOLECULE ACTIVATORS ; CELL-SURVIVAL ; TRANSCRIPTION FACTORS ; P53 ACETYLATION ; DEACETYLASE ; NICOTINAMIDE ; RESTRICTION ; REGULATOR ; DISCOVERY ; SIRTINOL |
| 资助项目 | CAS[00000000] ; National Science Fund for Creative Research Groups[21021063] ; Science and Technology Commission of Shanghai Municipality[08JC1422100] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000316242700044 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277738]  |
| 专题 | 药物化学研究室 药理学第三研究室 |
| 通讯作者 | Xu, Ming-Hua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Pharmacol 3, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Jiahui,Li, Yi,Chen, Kaixian,et al. Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2013,60:441-450. |
| APA | Wu, Jiahui,Li, Yi,Chen, Kaixian,Jiang, Hualiang,Xu, Ming-Hua,&Liu, Dongxiang.(2013).Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,60,441-450. |
| MLA | Wu, Jiahui,et al."Identification of benzofuran-3-yl(phenyl)methanones as novel SIRT1 inhibitors: Binding mode, inhibitory mechanism and biological action".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 60(2013):441-450. |
入库方式： OAI收割
来源：上海药物研究所
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