Design, synthesis, and bioevaluation of benzamides: novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Aß aggregation, and ß-secretase.
Bioorg Med Chem
; 20(22): 6739-50, 2012 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-23041347
ABSTRACT
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 6.47nM against human AChE. Particularly, it showed simultaneous inhibitory effects against BChE, Aß aggregation, and ß-secretase. We therefore conclude that compound 2e is a very promising multi-function lead for the treatment of AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Quinolínio
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Benzamidas
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Butirilcolinesterase
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Desenho de Fármacos
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Inibidores da Colinesterase
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Peptídeos beta-Amiloides
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Secretases da Proteína Precursora do Amiloide
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article