Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.
J Enzyme Inhib Med Chem
; 34(1): 631-637, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-30727776
ABSTRACT
A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acetilcolinesterasa
/
Butirilcolinesterasa
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Inhibidores de la Colinesterasa
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Cumarinas
/
Descubrimiento de Drogas
/
Antioxidantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article