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Current Trends in Medicinal Chemistry   Volumes    Volume 7 
Antidiabetic effects of sulfonamide derivatives based on structural fragment of sulfonylureas
Marisa Jádna Silva Frederico, Alessandra Mascarello, Allisson Jhonatan Gomes Castro, Camila Pires Mendes, Virgínia Demarchi Kappel, Luisa Helena Cazarolli, Ziliani da Silva Buss, Taisa Regina Stumpf, Rosendo Augusto Yunes, Ricardo José Nunes, Fátima Regina Mena Barreto Silva
Pages: 11 - 25
Number of pages: 15
Current Trends in Medicinal Chemistry
Volume 7 

Copyright © 2013 Research Trends. All rights reserved

The purpose of this study was to investigate the antidiabetic effect of sulfonamide derivatives based on a glibenclamide fragment using the bioisosterism strategy. The antihyperglycemic effects of sulfonamide derivatives were investigated and the glycemia, insulin secretion, calcium uptake, glycogen content, intestinal disaccharidase and lactate dehydrogenase activities were evaluated. The sulfonamide 5, substituted with the 4-OCH3-phenyl group, improved glucose tolerance and induced insulin secretion. In addition, this sulfonamide stimulated calcium influx in pancreatic islet. The stimulatory effect of sulfonamide 5 on calcium uptake is mediated by ATP-dependent K+ channels, L-type voltage-dependent calcium channels, intracellular calcium and protein kinase C in pancreatic islet cells. Additional targets involved in glucose homeostasis were studied in the presence of sulfonamide 5. In the intestine, this compound inhibited maltase and sucrose activity and in skeletal muscle increased glycogen content. The toxicity of sulfonamide 5 was not detected by LDH assay. As a whole, the sulfonamide 5 contributes to glucose homeostasis by acting at multiple tissues involved in glucose metabolism. The pharmacological profile of sulfonamide 5 showed that it might be useful in the treatment of diabetes both as an insulin secretagogue and an insulinomimetic agent.
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