New Quinazoline-Sulfonylurea Conjugates: Design, Synthesis and Hypoglycemic Activity
| Autor: | AlShaimaa M. Taha, Sahar M. Abou-Seri, Nour M Abdel-Kader, Mona A. Mohamed |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
medicine.drug_class medicine.medical_treatment Glucose uptake Down-Regulation 030209 endocrinology & metabolism Pharmacology 030226 pharmacology & pharmacy Diabetes Mellitus Experimental Rats Sprague-Dawley Glibenclamide Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Alloxan Glyburide Drug Discovery medicine Animals Hypoglycemic Agents Insulin Muscle Skeletal Pancreas Glucose Transporter Type 2 Glucose Transporter Type 4 Molecular Structure biology Chemistry Glucose transporter medicine.disease Sulfonylurea Up-Regulation Insulin receptor Insulin Receptor Substrate Proteins Quinazolines biology.protein Female Gliquidone medicine.drug |
| Zdroj: | Medicinal Chemistry. 15:634-647 |
| ISSN: | 1573-4064 |
| DOI: | 10.2174/1573406415666181208104543 |
| Popis: | Background:Sulphonylureas are the oldest and commonly used to treat diabetic patients, but its efficacy declines by time. It was reported that quinazoline nucleus exhibits a potent hypoglycemic effect in diabetic animal models.Objective:The current study aimed to synthesize new quinazoline-sulfonylurea conjugates and evaluate their hypoglycemic effects in alloxan-induced diabetic rats.Methods:The conjugates were synthesized by bioisosteric replacement of 5-chloro-2-methoxybenzamide moiety in glibenclamide or 1,3-dioxo-3,4-dihydroisoquinoline moiety in gliquidone with 6,7-dimethoxy-4-oxoquinazoline moiety (compounds 4a-4d, 9b-9c and 10b-10d). Diabetes was induced in rats by a single i.p. administration of alloxan, followed by treatment with the synthesized conjugates (5mg/kg Body weight).Results:All conjugates showed hypoglycemic effects with different efficacy indicated by the reduction in blood glucose and elevation of insulin levels. Moreover, these conjugates up-regulated the expression of pancreatic glucose transporter 2, muscle glucose transporter 4, and insulin receptor substrate-1 genes, compared to the diabetic group. A normal pancreatic tissue pattern was noticed in diabetic rats treated with compounds 9b, 9c, and 10c.Conclusion:Conjugation of sulfonylurea with quinazoline (especially 9b, 9c, 10c) possessed a significant hypoglycemic effect through improving blood insulin level and insulin action and consequently increased the glucose uptake by the skeletal muscles. |
| Databáze: | OpenAIRE |
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