期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 139, 期 -, 页码 280-289出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.07.072
关键词
Alzheimer's disease; Acetylcholinesterase; Neuroprotective activity; Tacrine; Phthalazine; beta-amyloid aggregation
资金
- Tehran University of Medical Sciences and Health Services
- Iran National Science Foundation
A novel series of tacrine-like compounds 7a-u possessing a fused pyrazolo[1,2-b]phthalazine structure were designed and synthesized as potent and selective inhibitors of AChE. The in-vitro biological assessments demonstrated that several compounds had high anti-AChE activity at nano-molar level. The more promising compound 71 with IC50 of 49 nM was 7-fold more potent than tacrine and unlike tacrine, it was highly selective against AChE over BuChE. The cell-based assays against hepatocytes (HepG2) and neuronal cell line (PC12) revealed that 71 had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H2O2-induced damage in PC12 cells. This compound could also inhibit AChE-induced and self-induced A beta peptide aggregation. The advantages including synthetic accessibility, high potency and selectivity, low toxicity, adjunctive neuroprotective and A beta aggregation inhibitory activity, make this compound as a new multifunctional lead for Alzheimer's disease drug discovery. (C) 2017 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据