Discovery, synthesis, and structure activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPK alpha 2 beta 1 gamma 1 activators
文献类型：期刊论文
| 作者 | Liu, Junhua2; Chen, Dakai2; Liu, Peng1; He, Mengna2; Li, Jia2 ; Li, Jingya2; Hu, Lihong2
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2014-05-22 |
| 卷号 | 79页码:340-349 |
| 关键词 | 20(S)-Protopanoxadiol AMPK AMPK heterotrimer alpha 2 beta 1 gamma 1 Activators Structure-activity relationship |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2014.04.010 |
| 文献子类 | Article |
| 英文摘要 | Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype alpha 2 beta 1 gamma 1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure activity relationship study showed that the amine derivatives at the 24-position (groups 1 VI) can improve the potency (EC50: 0.7-2.3 mu M) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 12 and 0.7 mu M) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. (C) 2014 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | PROTEIN-KINASE ; SIGNALING PATHWAYS ; METABOLIC SYNDROME ; PANAX-GINSENG ; HEPG2 CELLS ; RAT-LIVER ; AMPK ; EXTRACT ; GINSENOSIDES ; IDENTIFICATION |
| 资助项目 | National Natural Science Foundation of China[81273397] ; National Natural Science Foundation of China[81125023] ; National Natural Science Foundation of China[81273566] ; Chinese National Science & Technology Major Project[2013ZX09508104] ; Chinese National Science & Technology Major Project[2012ZX09103-101-018] ; Chinese National Science & Technology Major Project[2014ZX09301-306-03] ; Science Foundation of Shanghai[12XD1405700] ; Science Foundation of Shanghai[13DZ2290300] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000336700600032 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277070]  |
| 专题 | 国家新药筛选中心 上海中药现代化研究中心 |
| 通讯作者 | Li, Jingya |
| 作者单位 | 1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Liu, Junhua,Chen, Dakai,Liu, Peng,et al. Discovery, synthesis, and structure activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPK alpha 2 beta 1 gamma 1 activators[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2014,79:340-349. |
| APA | Liu, Junhua.,Chen, Dakai.,Liu, Peng.,He, Mengna.,Li, Jia.,...&Hu, Lihong.(2014).Discovery, synthesis, and structure activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPK alpha 2 beta 1 gamma 1 activators.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,79,340-349. |
| MLA | Liu, Junhua,et al."Discovery, synthesis, and structure activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPK alpha 2 beta 1 gamma 1 activators".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 79(2014):340-349. |
入库方式： OAI收割
来源：上海药物研究所
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