Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation.
Bioorg Med Chem
; 20(8): 2527-34, 2012 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-22444876
ABSTRACT
A series of isaindigotone derivatives and analogues were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced ß-amyloid (Aß) aggregation. The synthetic compounds had IC(50) values at micro or nano molar range for cholinesterase inhibition, and some compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE, which were much better than the isaindigotone derivatives previously reported by our group. Most of these compounds showed higher self-induced Aß aggregation inhibitory activity than a reference compound curcumin. The structure-activity relationship studies revealed that the derivatives with higher inhibition activity on AChE also showed higher selectivity for AChE over BuChE. Compound 6c exhibiting excellent inhibition for both AChE and self-induced Aß aggregation was further studied using CD, EM, molecular docking and kinetics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetilcolinesterase
/
Quinazolinas
/
Desenho de Fármacos
/
Inibidores da Colinesterase
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Peptídeos beta-Amiloides
/
Alcaloides
Tipo de estudo:
Evaluation_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article