Design, synthesis, and bioevaluation of benzamides: Novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Aβ aggregation, and β-secretase

被引：41

作者：

Peng, Da-Yong ^{[1
]}

Sun, Qi ^{[1
]}

Zhu, Xiao-Lei ^{[1
]}

Lin, Hong-Yan ^{[1
]}

Chen, Qiong ^{[1
]}

Yu, Ning-Xi ^{[1
]}

Yang, Wen-Chao ^{[1
]}

Yang, Guang-Fu ^{[1
]}

机构：

[1] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 22期

关键词：

Acetylcholinesterase; Alzheimer's disease; Benzamide; Structure-based design; TARGET-DIRECTED LIGANDS; BOUNDARY-ELEMENT METHOD; ALZHEIMERS-DISEASE; HIGHLY POTENT; CHOLINESTERASE-INHIBITORS; BINDING; BUTYRYLCHOLINESTERASE; DERIVATIVES; HYBRIDS; STRATEGIES;

D O I：

10.1016/j.bmc.2012.09.016

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：

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.

引用

页码：6739 / 6750

页数：12

共 57 条

[1] Design, Synthesis, and Qualitative Structure-Activity Evaluations of Novel β-Secretase Inhibitors as Potential Alzheimer's Drug Leads [J].