Synthesis and Investigating Hypoglycemic and Hypolipidemic Activities of Some Glibenclamide Analogues in Rats

Title:Synthesis and Investigating Hypoglycemic and Hypolipidemic Activities of Some Glibenclamide Analogues in Rats

Volume: 14 Issue: 2

Author(s): Abbas Ahmadi, Mohsen Khalili, Khadijeh Khatami, Majid Farsadrooh and Babak Nahri-Niknafs

Affiliation:

Keywords: Glibenclamide, Hypoglycemic and lipid-lowering effects, Sulfonylurea, Type 2 diabetes.

Abstract: Glibenclamide (5-chloro-N-(4-[N-(cyclohexylcarbamoyl) sulfamoyl] phenethyl)-2-methoxybenzamide, Glyburide, E) is a well-known and potent second-generation of sulfonylurea oral hypoglycemic drug which is most widely used in type 2 diabetes recently. It acts upon pancreatic β-cells by stimulating insulin secretion in glucose and lipid-lowering activities. So far, many derivatives of E have been synthesized by adding new structural moieties to its structure while preserving its binding affinity to the receptor before their anti-hyperglycemic and anti hyperlipidemic activities being evaluated. In this study, new analogues of E after changing lipophilic side chain (5-chloro-2-methoxy benzamide) with 4- bromo-3, 5-dimethoxy benzamide and 2, 4-dichloro benzamide were synthesized. Also, their glucose and lipid-lowering activities were evaluated and compared to E and Tolbutamide (a famous first-generation of sulfonylurea oral hypoglycemic drug) by the known procedures. Findings showed that chloride substitution on lipophilic side chain of Glibenclamide could possibly increase the affinity of drug for receptor/or its half life time that resulted in more lasting anti-hyperglycemic and anti lipidemic activities in diabetic rats. However, bromide substitution with additional methoxy groups in benzamide ring could slightly improve the anti-hyperglycemic potency of the new drug compared to the root drug (E).

Cite this article as:

Ahmadi Abbas, Khalili Mohsen, Khatami Khadijeh, Farsadrooh Majid and Nahri-Niknafs Babak, Synthesis and Investigating Hypoglycemic and Hypolipidemic Activities of Some Glibenclamide Analogues in Rats, Mini-Reviews in Medicinal Chemistry 2014; 14 (2) . https://dx.doi.org/10.2174/1570193X10666140103112311