Design, synthesis, biological evaluation, and docking study of chromone-based phenylhydrazone and benzoylhydrazone derivatives as antidiabetic agents targeting α-glucosidase.
Bioorg Chem
; 132: 106384, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36696731
ABSTRACT
To develop novel α-glucosidase inhibitors, a series of chromone-based phenylhydrazone and benzoylhydrazone derivatives were designed, synthesized, and evaluated their inhibitory effects on α-glucosidase. The target compounds were characterized using 1H NMR, 13C NMR, and high-resolution mass spectra. Some of the compounds showed a varying degree of α-glucosidase inhibitory activity with IC50 values ranging from 6.59 ± 0.09 to 158.55 ± 0.87 µM. Among them, compound 5c (IC50 = 6.59 ± 0.09 µM) was the most potent inhibitor by comparison with positive control acarbose (IC50 = 685.11 ± 7.46 µM). Enzyme kinetic, fluorescence analysis, circular dichroism spectra, and molecular docking techniques were employed to explain the underlying molecular mechanisms of 5c inhibition on α-glucosidase. In vivo sucrose-loading test showed that 5c could suppress the rise of blood glucose levels after loading sucrose in normal Kunming mice. The cytotoxicity assay indicated that 5c exhibited low cytotoxicity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alfa-Glucosidases
/
Hipoglicemiantes
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China