Synthesis and molecular docking studies of 5-trifluoromethoxy-2-indolinones as cholinesterase dual inhibitors.
Future Med Chem
; 16(7): 623-645, 2024 04.
Article
en En
| MEDLINE
| ID: mdl-38470247
ABSTRACT
Background:
In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease.Methods:
1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones (6-7) were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites.Results:
Compound 6g was the strongest inhibitor against both AChE (Ki = 0.35 µM) and BuChE (Ki = 0.53 µM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound 7m had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE (Ki = 0.69 µM) and BuChE (Ki = 0.95 µM).Conclusion:
The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de la Colinesterasa
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article