【文章名】Design, synthesis, and bioevaluation of benzamides: Novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, A beta aggregation, and beta-secretase
Design, synthesis, and bioevaluation of benzamides: Novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, A beta aggregation, and beta-secretase
作者
PENG DAYONG; SUN QI; ZHU XIAOLEI; LIN HONGYAN; CHEN QIONG; YU NINGXI; YANG WENCHAO; YANG GUANGFU
[摘要]：Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. In this study, we conducted a structure-based design and successfully produced a series of new multi-site AChE inhibitors with a novel framework. Compound 2e, characterized by a central benzamide moiety linked to an isoquinoline at one side and acetophenone at the other, was the most potent candidate with K-i of 6.47 nM against human AChE. Particularly, it showed simultaneous inhibitory effects against BChE, A beta aggregation, and beta-secretase. We therefore conclude that compound 2e is a very promising multi-function lead for the treatment of AD. (C) 2012 Elsevier Ltd. All rights reserved.
