Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase
文献类型：期刊论文
| 作者 | Zhu, Yiping1; Xiao, Kun1; Ma, Lanping1 ; Xiong, Bin1; Fu, Yan1; Yu, Haiping2; Wang, Wei1; Wang, Xin1; Hu, Dingyu1; Peng, Hongli1
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2009-02-15 |
| 卷号 | 17期号:4页码:1600-1613 |
| 关键词 | AD AChE BACE-1 Dual inhibitor HE HMC HEA |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2008.12.067 |
| 文献子类 | Article |
| 英文摘要 | To explore novel effective drugs for the treatment of Alzheimer's disease (AD), a series of dual inhibitors of acetylcholineterase (AChE) and beta-secretase (BACE-1) were designed based on the multi-target-directed ligands strategy. Among them, inhibitor 28 exhibited good dual potency in enzyme inhibitory potency assay (BACE-1: IC50 = 0.567 mu M; AChE: IC50 = 1.83 mu M), and also showed excellent inhibitory effects on Ab production of APP transfected HEK293 cells (IC50 = 98.7 nM) and mild protective effect against hydrogen peroxide (H2O2)-induced PC12 cell injury. Encouragingly, intracerebroventricular injection of 28 into amyloid precursor protein (APP) transgenic mice caused a 29% reduction of A beta(1-40) production. Therefore, 28 was demonstrated as a good lead compound for the further study and more importantly, the strategy of AChE and BACE-1 dual inhibitors might be a promising direction for developing novel drugs for AD patients. (c) 2009 Elsevier Ltd. All rights reserved. |
| WOS关键词 | COMBAT ALZHEIMERS-DISEASE ; TARGET-DIRECTED LIGANDS ; X-RAY-STRUCTURE ; POTENT INHIBITORS ; POLYAMINE BACKBONE ; BACE1 INHIBITORS ; ANTIACETYLCHOLINESTERASE ACTIVITY ; PEPTIDOMIMETIC INHIBITORS ; COUMARIN DERIVATIVES ; AMYLOID AGGREGATION |
| 资助项目 | National Natural Science Foundation of China[30230400] ; National Natural Science Foundation of China[30672538] ; National Natural Science Foundation of China[30572169] ; Ministry of Science and Technology of China[2004CB518907] ; '863' Hi-Tech Program of China[2004 AA2 Z3781] ; State Key Program of Basic Research of China[2004GB518907] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000263502300022 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279311]  |
| 专题 | 药理学第二研究室 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 药物化学研究室 国家新药筛选中心 |
| 通讯作者 | Zhang, Haiyan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Natl Ctr Drug Screening, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhu, Yiping,Xiao, Kun,Ma, Lanping,et al. Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2009,17(4):1600-1613. |
| APA | Zhu, Yiping.,Xiao, Kun.,Ma, Lanping.,Xiong, Bin.,Fu, Yan.,...&Shen, Jingkang.(2009).Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase.BIOORGANIC & MEDICINAL CHEMISTRY,17(4),1600-1613. |
| MLA | Zhu, Yiping,et al."Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase".BIOORGANIC & MEDICINAL CHEMISTRY 17.4(2009):1600-1613. |
入库方式： OAI收割
来源：上海药物研究所
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