Title:Sulfonyl Group-Containing Compounds in the Design of Potential Drugs for the Treatment of Diabetes and Its Complications
VOLUME: 19 ISSUE: 21
Author(s):X. Chen, S. Hussain, S. Parveen, S. Zhang, Y. Yang and C. Zhu
Affiliation:Department of Applied Chemistry, Beijing Institute of Technology, No.5, Zhongguancun South Street, 100081 Beijing, China.
Keywords:Sulfonyl group, diabetes, glucose metabolism, insulin secretion/resistance, diabetic complications, inhibitors, activators
Abstract:Sulfonyl group-containing compounds constitute an important class of therapeutical agents in medicinal chemistry presumably
because of the tense chemical structure and functionality of the sulfonyl, which could not only form hydrogen bonding interactions with
active site residues of biological targets but also, as incorporated into core ring structure, constrain the side chains and allowed their
specific conformations that fit the active sites. This review focuses on sulfonamides and sulfones, which cover more than 40 series and
are associated with at least 10 potential pharmaceutical targets in pathways of glucose metabolism and insulin signaling. A large number
of such compounds have been reported as pharmaceuticals every year in the last decade. In particular, increasing studies suggest that
sulfonamides and sulfones play a key role in the design of pharmaceutical agents with potential application for the treatment of diabetes
and its complications. First, they are inhibitors of a variety of enzymes including 11β-hydroxysteroid dehydrogenase type 1, α-
glucosidase, carnitine palmitoyltransferase and cytosolic phosphoenolpyruvate carboxykinase, and in turn involved in the regulation of
the metabolism of glucose. In addition, they are active as activators of glucokinase and as antagonists of ghrelin receptors. These enzyme
and receptors are tightly associated with the regulation of glucose metabolism and the improvement of insulin resistance. Secondly,
sulfonamides and sulfones act in the insulin secretion. As agonists, they activate insulin receptor tyrosine kinase and thus increase insulin
sensitivity. Moreover, they as inhibitors suppress protein tyrosine phosphatase 1B and dipeptidyl peptidase IV, and thus normalize the
insulin signaling pathway. Finally, a number of sulfonamides and sulfones are inhibitors of aldose reductase, which have been linked to
diabetic complications.
