Thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors: Synthesis, inhibitory activity, binding interaction and hypoglycemic activity.
Bioorg Chem
; 144: 107177, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38335756
ABSTRACT
In order to find effective α-glucosidase inhibitors, a series of thiazolidine-2,4-dione derivatives (C1 â¼ 36) were synthesized and evaluated for α-glucosidase inhibitory activity. Compared to positive control acarbose (IC50 = 654.35 ± 65.81 µM), all compounds (C1 â¼ 36) showed stronger α-glucosidase inhibitory activity with IC50 values of 0.52 ± 0.06 â¼ 9.31 ± 0.96 µM. Among them, C23 with the best anti-α-glucosidase activity was a reversible mixed-type inhibitor. Fluorescence quenching suggested the binding process of C23 with α-glucosidase in a static process. Fluorescence quenching, CD spectra, and 3D fluorescence spectra results also implied that the binding of C23 with α-glucosidase caused the conformational change of α-glucosidase to inhibit the activity. Molecular docking displayed the binding interaction of C23 with α-glucosidase. Compound C23 (8 â¼ 64 µM) showed no cytotoxicity against LO2 and 293 cells. Moreover, oral administration of C23 (50 mg/kg) could reduce blood glucose and improve glucose tolerance in mice.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiazolidinediones
/
Glycoside Hydrolase Inhibitors
/
Hypoglycemic Agents
Limits:
Animals
Language:
En
Journal:
Bioorg Chem
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States