Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment

被引：23

作者：

Zheng, Yunxiaozhu ^{[1
]}

Qiang, Xiaoming ^{[1
]}

Xu, Rui ^{[1
]}

Song, Qing ^{[1
]}

Tian, Chaoquan ^{[1
]}

Liu, Hongyan ^{[1
]}

Li, Wei ^{[1
]}

Tan, Zhenghuai ^{[2
]}

Deng, Yong ^{[1
]}

机构：

[1] Sichuan Univ, Dept Med Chem, Key Lab Drug Targeting & Drug Delivery Syst, Educ Minist,West China Sch Pharm, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Acad Chinese Med Sci, Inst Tradit Chinese Med Pharmacol & Toxicol, Chengdu 610041, Sichuan, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2018年 / 78卷

关键词：

Alzheimer's disease; Pterostilbene beta-amino alcohol derivatives; Acetylcholinesterase inhibitors; A beta aggregation inhibitors; Neuroprotective effects; Multifunctional agents; MANNICH BASE DERIVATIVES; AMYLOID AGGREGATION; DUAL INHIBITORS; NEUROPROTECTIVE PROPERTIES; IN-VITRO; ACETYLCHOLINESTERASE; HYBRIDS; ANTIOXIDANT; BUTYRYLCHOLINESTERASE; THERAPEUTICS;

D O I：

10.1016/j.bioorg.2018.03.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of pterostilbene beta-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50 = 24.04 mu M), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced A beta(1-42) aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a promising candidate for further studies directed to the development of novel drugs against AD. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：298 / 306

页数：9

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