Design, Synthesis and in Vivo Evaluation of Novel Glycosylated Sulfonylureas as Antihyperglycemic Agents

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 11; pp. 20063 - 20078
• Main Authors: Suaifan, Ghadeer A R Y, Shehadeh, Mayadah B, Darwish, Rula M, Al-Ijel, Hebah, Abbate, Vincenzo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.11.2015; MDPI
• Subjects: Animals; Anorexia; antihyperglycemic agents; Antiparasitic agents; Blood Glucose - drug effects; Cancer; Chemistry Techniques, Synthetic; Diabetes; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diuretics; Drug Design; Drug dosages; Drug Evaluation, Preclinical; Gastroesophageal reflux; glucosamine; Glucose; Glycosylation; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Insulin; Malaria; Male; Mice; Molecular Structure; Oral administration; Pharmaceuticals; Pharmacy; streptozocine; Sulfonylurea Compounds - chemical synthesis; Sulfonylurea Compounds - chemistry; Sulfonylurea Compounds - pharmacology; sulphonylurea; glucosamine; streptozocine; antihyperglycemic agents; sulphonylurea
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules201119676

Sulphonylurea compounds have versatile activities such as antidiabetic, diuretic, herbicide, oncolytic, antimalarial, antifungal and anticancer. The present study describes the design, synthesis and in vivo testing of novel glycosylated aryl sulfonylurea compounds as antihyperglycaemic agents in streptozocine-induced diabetic mice. The rational for the introduction of the glucosamine moiety is to enhance selective drug uptake by pancreatic β-cells in order to decrease the cardiotoxic side effect commonly associated with sulfonylurea agents. 2-Deoxy-2-(4-chlorophenylsulfonylurea)-D-glucopyranose was found to be the most potent antihyperglycaemic agents among the synthesized compounds in diabetic mice. This investigation indicates the importance of this novel class as potential antihyperglycaemic agents.