New Selective Inhibitors of α‐Glucosidase for the Treatment of Type 2 Diabetes Mellitus

Abstract

AbstractType 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post‐prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α‐amylase and α‐glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α‐amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α‐glucosidase with low micromolar IC50 (3.64‐7.98 μM) compared to the acarbose (IC50 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α‐amylase (IC50>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α‐glucosidase, which support the existence of both active site and allosteric interactions.