Discovery of New α-Glucosidase Inhibitors: Structure-Based Virtual Screening and Biological Evaluation.
Front Chem
; 9: 639279, 2021.
Article
en En
| MEDLINE
| ID: mdl-33763406
ABSTRACT
α-Glycosidase inhibitors could inhibit the digestion of carbohydrates into glucose and promote glucose conversion, which have been used for the treatment of type 2 diabetes. In the present study, 52 candidates of α-glycosidase inhibitors were selected from commercial Specs compound library based on molecular docking-based virtual screening. Four different scaffold compounds (7, 22, 37, and 44) were identified as α-glycosidase inhibitors with IC50 values ranging from 9.99 to 35.19 µM. All these four compounds exerted better inhibitory activities than the positive control (1-deoxynojirimycin, IC50 = 52.02 µM). The fluorescence quenching study and kinetic analysis revealed that all these compounds directly bind to α-glycosidase and belonged to the noncompetitive α-glycosidase inhibitors. Then, the binding modes of these four compounds were carefully investigated. Significantly, these four compounds showed nontoxicity (IC50 > 100 µM) toward the human normal hepatocyte cell line (LO2), which indicated the potential of developing into novel candidates for type 2 diabetes treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Front Chem
Año:
2021
Tipo del documento:
Article
País de afiliación:
China