Alpha-glucosidase inhibitory and hypoglycemic effects of imidazole-bearing thioquinoline derivatives with different substituents: In silico, in vitro, and in vivo evaluations.
Bioorg Chem
; 144: 107106, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38244380
ABSTRACT
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Nitroimidazóis
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article