文献类型：期刊文献

英文题名：Design, synthesis and biological evaluation of 3-piperazinecarboxylate sarsasapogenin derivatives as potential multifunctional anti-Alzheimer agents

作者：Yang, Gui-Xiang[1];Ge, Song-Lan[1];Wu, Yan[1];Huang, Jin[1];Li, Shi-Liang[1];Wang, Rui[1];Ma, Lei[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2018

卷号：156

起止页码：206

外文期刊名：EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000443663200017)】；

基金：This work was supported by National Natural Science Foundation of China (81673318); and Shanghai Biomedical Technology Support Program (15401901100).

语种：英文

外文关键词：Sarsasapogenin derivatives; Alzheimer's disease; Antioxidation; Antiinflammation; Structure-activity relationship; Beta-amyloid

摘要：A series of multifunctional 3-piperazinecarboxylate sarsasapogenin derivatives were designed and synthesized against Alzheimer's disease (AD). The protection against H2O2-triggered oxidative stress in PC12 cells, and inhibition on LPS-induced NO production in RAW264.7 cell lines in vitro by these derivatives were firstly evaluated. Most of the compounds showed better antioxidant and antiinflammatory activities compared with sarsasapogenin, especially AA34 and AA36. Structure-activity relationships revealed that benzyl group, electron-donating group and intramolecular hydrogen bond might be beneficial to enhancing their neuroprotective activities. Moreover, A beta 42 was the optimum predicted target based on the high 3D molecular similarity between compound AA36 and caprospinol. In the following experiments, AA36 significantly protected PC12 cells from A beta-induced damage and improved learning and memory impairments in A beta-injected mice. Thus AA36 is regarded as a potent anti-AD agent and N-substituted piperazinecarboxylate can be served as a promising structural unit for anti-AD drug design. (C) 2018 Published by Elsevier Masson SAS.