Synthesis and alpha-amylase inhibition of some resveratrol derivatives

One of the most common metabolic disorder of the twenty-first century is the diabetes (type 1 and 2) characterized by high blood sugar levels related to alterations in glucose and lipid metabolism. [1] Stilbenoids, a class of natural products whose main exponent is resveratrol, have been increasingly getting popularity for their wide spectrum of biological activities and the peculiar molecular structures. In particular, different studies have demonstrated antidiabetic effects of resveratrol through different mechanism, one of these is the inhibition of pancreatic α-amylase. [2] Pancreatic α-amylase is an endo-hydrolase, acting on 1,4-glucosidic linkages in linear regions of suitable length in starch, glycogen, and various oligosaccharides. The activity of the enzyme releases absorbable simpler sugars, readily available for intestinal absorption. Inhibiting the α-amylase activity, the presence of oligosaccharides and absorbable sugars decreases considerably. [3] Our study is focused on the investigation of the hypoglycaemic potential of resveratrol derivatives as α-amylase inhibitors. To this aim, we have synthesized a collection of monomers and dimers belonging to the stilbenoids family, and we have tested them as single molecules against α-amylase. Notably, we have found that some dimeric compounds (i.e. viniferins) were more active than the standard compound, acarbose. Moreover, in order to perform preliminary structure-activity relationship (SAR) studies on this class of compounds, starting from the structures of viniferins, we have designed and synthesized a number of simplified analogues, to be tested as α-amylase inhibitors. References: 1. Cho et al, Diabetes Research and Clinical Practice, 138, 271-281, 2018 2. Oyenthi et al., Journal of Diabetes Research, 9737483, 2016 3. Fujisawa et al., Metabolism Clinical and Experimental, 54, 387-390, 2005