Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity.
Bioorg Chem
; 143: 107059, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38154388
ABSTRACT
This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a Ki value of 2.61 µM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Inibidores de Glicosídeo Hidrolases
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article