Ceanothanes Derivatives as Peripheric Anionic Site and Catalytic Active Site Inhibitors of Acetylcholinesterase: Insights for Future Drug Design.
Int J Mol Sci
; 25(13)2024 Jul 03.
Article
em En
| MEDLINE
| ID: mdl-39000410
ABSTRACT
Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system and particularly in the formation of amyloid plaques; therefore, the inhibition of AChE has become one of the most promising strategies for the treatment of AD, particularly concerning AChE inhibitors that interact with the peripheral anionic site (PAS). Ceanothic acid isolated from the Chilean Rhamnaceae plants is an inhibitor of AChE through its interaction with PAS. In this study, six ceanothic acid derivatives were prepared, and all showed inhibitory activity against AChE. The structural modifications were performed starting from ceanothic acid by application of simple synthetic routes esterification, reduction, and oxidation. AChE activity was determined by the Ellmann method for all compounds. Kinetic studies indicated that its inhibition was competitive and reversible. According to the molecular coupling and displacement studies of the propidium iodide test, the inhibitory effect of compounds would be produced by interaction with the PAS of AChE. In silico predictions of physicochemical properties, pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of the ceanothane derivatives were performed using the Swiss ADME tool.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
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Desenho de Fármacos
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Inibidores da Colinesterase
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Domínio Catalítico
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Suíça