Affiliation:
1. LG2A UR 7378 Université de Picardie Jules Verne, 33 rue St Leu 80039 Amiens Cedex France
2. Faculté des Sciences de Bizerte Laboratoire d'Application de la Chimie aux Ressources et Substances Naturelles et à l'Environnement (LACReSNE) LR05ES09 Unité « Interactions Moléculaires Spécifiques » Université de Carthage Faculty of Sciences of Bizerte TN 7021 Zarzouna-Bizerte Tunisie
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.