Natural polyphenols and synthetic analogues as potential hypoglycemic agents

In the last decade the search for new and effective antidiabetic drugs has rapidly grown, in view of the epidemic diffusion of diabetes mellitus, a chronic metabolic disease associated with disorders of carbohydrate metabolism and characterized by hyperglycemia. The control of postprandial blood glucose excursions has come to the fore of the treatment of diabetes. One of the therapeutic approaches to reduce postprandial hyperglycemia is to retard digestion and absorption of dietary carbohydrates by inhibiting digesting enzymes, such as α-glucosidase and α-amylase, in the digestive organs. The mechanism of α-glucosidase inhibition represents the pharmacological optimization of the dietary principle of delayed carbohydrate absorption. Furthermore, the treatment with α-glucosidase inhibitors does not only could improve the metabolic state but it has also the potential to delay, or possibly prevent, the development of diabetic complications. As a new class of α-glucosidase inhibitors, natural polyphenols are attracting great interest as potential hypoglycemic agents, alternative or coadiuvants to the currently employed drugs, to prevent and treat diabetes and obesity.Recently some efforts have been devoted from our group to investigate natural polyphenolsfrom Quercus roburand Castanea sativaas inhibitors of yeast α-glucosidase, the enzyme most frequently employed in the preliminary steps of the search for new antidiabetic drugs; in addition, we also evaluated as potential hypoglycemic agents synthetic analogues of natural polyphenols: promising results were obtained with resveratrol-related glycosides and  especially with dimeric neolignans inspired by magnolol.

The goal of this research activity is the extension of these studies to develop new α-glucosidase inhibitors, both of natural or synthetic origin.  Thus, we’ll examine further plant extracts, in particular those rich in polyphenols, and we are also planning the synthesis of new molecules preferably employing biomimetic, enzyme-catalyzed reactions or benign chemical reagents. The molecular structure of the compounds under study will be confirmed mainly by an extensive use of NMR spectral analysis (mono- and two-dimensional experiments); subsequently the compounds will be evaluated for α-glucosidase inhibition activity with spectrophotometric methods. 

Scientific Responsible: Prof. Corrado Tringali (e-mail: ctringali@unict.it)