Rosmarinic acid amides: synthesis, α-glucosidase inhibition and enzyme binding mode

Introduction: The -glucosidase is involved in the final step of the carbohydrates digestion. In diabetes mellitus patients, it results in a rapid rise in blood glucose levels (hyperglycemia), an event normally associated with the production of reactive radical species1 and frequent development of diabetes-related pathologies. -Glucosidase inhibition is an established protocol for diabetes therapy, but the current antidiabetic drugs show certain side effects, thus increasing the search of -glucosidase inhibitors of natural origin. Many natural products have been reported for their potential antidiabetic activity and most of them are polyphenols2 with antioxidative properties. Among these, rosmarinic acid (RA)3 and some phenolic amides have shown -glucosidase inhibition.4 The objective of this study was to evaluate a small library of rosmarinic acid amides as potential inhibitors of yeast -glucosidase. Their antioxidant activity was also measured. Materials & Methods: The amides were synthesized starting from RA and aliphatic- and alkyl aryl-amines after the previous activation with EDCI/HOBt. Results: Some amides were more active than both RA and the antidiabetic drug acarbose. A molecular docking study was also carried out on the yeast -glucosidase to highlight the putative binding mode. Conclusion: This work would be significant for the search of new effective -glucosidase inhibitors.