Synthesis of new clioquinol derivatives as potent α-glucosidase inhibitors; molecular docking, kinetic and structure-activity relationship studies.
Bioorg Chem
; 119: 105506, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34896920
ABSTRACT
Diabetes mellitus is a chronic metabolic disorder with increasing prevalence and long-term complications. The aim of this study was to identify α-glucosidase inhibitory compounds with potential anti-hyperglycemic activity. For this purpose, a series of new clioquinol derivatives 2a-11a was synthesized, and characterized by various spectroscopic techniques. The enzyme inhibitory activities of the resulting derivatives were assessed using an in-vitro mechanism-based assay. All the tested compounds 2a-11a of the series showed a significant α-glucosidase inhibition with IC50 values 43.86-325.81 µM, as compared to the standard drug acarbose 1C50 875.75 ± 2.08 µM. Among them, compounds 4a, 5a, 10a, and 11a showed IC50 values of 105.51 ± 2.41, 119.24 ± 2.37, 99.15 ± 2.06, and 43.86 ± 2.71 µM, respectively. Kinetic study of the active analogues showed competitive, non-competitive, and mixed-type inhibitions. Furthermore, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of α-glucosidase enzyme. The results indicate that these compounds have the potential to be further studied as new anti-diabetic agents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Clioquinol
/
Alpha-Glucosidases
/
Molecular Docking Simulation
/
Glycoside Hydrolase Inhibitors
/
Hypoglycemic Agents
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2022
Type:
Article
Affiliation country:
Pakistan