Synthesis, in vitro and in silico screening of 2-amino-4-aryl-6-(phenylthio) pyridine-3,5-dicarbonitriles as novel α-glucosidase inhibitors.
Bioorg Chem
; 100: 103879, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32413625
ABSTRACT
Inhibition of α-glucosidase enzyme is of prime importance for the treatment of diabetes mellitus (DM). Apart of many organic scaffolds, pyridine based compounds have previously been reported for wide range of bioactivities. The current study reports a series of pyridine based synthetic analogues for their α-glucosidase inhibitory potential assessed by in vitro, kinetics and in silico studies. For this purpose, 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 1-28 were synthesized and subjected to in vitro screening. Several analogs, including 1-3, 7, 9, 11-14, and 16 showed many folds increased inhibitory potential in comparison to the standard acarbose (IC50 = 750 ± 10 µM). Interestingly, compound 7 (IC50 = 55.6 ± 0.3 µM) exhibited thirteen-folds greater inhibition strength than the standard acarbose. Kinetic studies on most potent molecule 7 revealed a competitive type inhibitory mechanism. In silico studies have been performed to examine the binding mode of ligand (compound 7) with the active site residues of α-glucosidase enzyme.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Piridinas
/
Inibidores de Glicosídeo Hidrolases
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Paquistão