期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 23, 期 5, 页码 911-923出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.01.042
关键词
Alzheimer's disease; Chromone-2-carboxamido-alkylbenzylamines; Acetylcholinesterase inhibitors; Anti-oxidative activity; Biometal chelators; Ab aggregation inhibitors
资金
- Chinese National Natural Science Foundation [20872099]
- Research Fund for the Doctoral Program of Higher Education [20110181110079]
- Sichuan Academic and Technical Leader Training Foundation [2012DTP Y003]
- National Science and Technology Major Project on 'Key New Drug Creation and Manufacturing Program' [2013ZX 09301304-002]
A series of chromone-2-carboxamido-alkylbenzylamines were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good multifunctional activities. Among them, compound 49 displayed excellent inhibitory potency toward acetylcholinesterase (AChE), moderate anti-oxidative activity, selective biometal chelating, and possessed good inhibitory effects on self-induced and Cu2+-induced Ab aggregation. Both kinetic analysis of AChE inhibition and molecular modeling study indicated that 49 was a mixed-type inhibitor, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. These results suggested that 49 might be a potential multifunctional agent for AD treatment. (C) 2015 Elsevier Ltd. All rights reserved.
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