Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core.
Arch Pharm (Weinheim)
; 351(5): e1800024, 2018 May.
Article
em En
| MEDLINE
| ID: mdl-29611620
ABSTRACT
With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 µM and 20.2 ± 0.9 µM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Acetilcolinesterase
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Inibidores da Colinesterase
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Benzoxazinas
Limite:
Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Chile