Oxindole-Based α-Glucosidase Inhibitors: A Comprehensive Review

Abstract

α-Glucosidase is a crucial therapeutic target in type 2 diabetes mellitus due to its key role in carbohydrate metabolism, making the inhibition of this enzyme an effective strategy to control postprandial hyperglycaemia. Currently prescribed α-glucosidase inhibitors, such as Acarbose, Miglitol, and Voglibose, slow down glucose absorption and help manage blood sugar levels. However, their clinical use often limited by undesirable gastrointestinal side effects. Therefore, there is a need to develop more safer and effective alternatives. In recent years, oxindole-based derivatives have emerged as a highly promising scaffold for the development of new α-glucosidase inhibitors. These compounds offer remarkable structural diversity, a favourable pharmacological profile, and excellent potential for structural optimization. Advances in this area have focused on the synthesis, design, and biological evaluation of oxindole derivatives. The structure–activity relationship (SAR) studies showing that specific substitutions on the oxindole core can significantly enhance inhibitory potency. Hybridization of oxindoles with heterocyclic systems such as thiazoles, oxadiazoles, and spiro frameworks has further improved biological activity and drug-like properties. Molecular docking studies have provided valuable mechanistic insights into the binding interactions within the α-glucosidase active site, enabling more rational and targeted drug design. Overall, oxindole scaffolds are highly promising chemical class that holds significant potential to yield next-generation α-glucosidase inhibitors.