Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease.
Bioorg Med Chem Lett
; 23(9): 2636-41, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23511019
ABSTRACT
A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aß aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aß aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
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Flavonoides
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Desenho de Fármacos
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Inibidores da Colinesterase
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article