Dual α-amylase and α-glucosidase inhibitors: recent progress from natural and synthetic resources

Diabetes mellitus (DM) is a chronic metabolic disorder characterised by elevated blood glucose levels resulting from insufficient insulin production or insulin resistance. Its global prevalence has surged, particularly in low- and middle-income countries, with over 830 million affected. In recent years, dual inhibition of α-amylase and α-glucosidase, the enzymes involved in the metabolism of complex polysaccharides, has gained visibility in anti-diabetic medication research. The inhibition of these enzymes is responsible for reducing postprandial hyperglycemia. FDA-approved drugs, acarbose, voglibose, and miglitol, are effective but have serious side effects. Many research papers from various research groups have appeared in different databases, from natural to synthetic resources, describing the dual inhibition of α-amylase and α-glucosidase. However, none of the molecules have advanced to clinical development. The current review focuses on compiling an exhaustive report of novel molecules derived from synthetic and natural resources that act as dual α-amylase and α-glucosidase inhibitors. The review also highlights their biological activity, selectivity, structure-activity relationship, molecular docking, and mechanistic studies. A special emphasis on drug-designing strategies has also been given in the manuscript. The comprehensive compilation of research work in the field will provide an inevitable scope for designing and developing novel adenosine inhibitors with improved selectivity and efficacy.