Benzothiazole derivatives as effective α-glucosidase inhibitors: an insight study of structure-activity relationships and molecular targets

Abstract

In treating the major metabolic disorder diabetes mellitus type-2, the α-glucosidase enzyme inhibitors play an effective role due to their vital capability of polysaccharide hydrolyzation. A well-known α-glucosidase inhibitor drug such as acarbose and miglitol can provide in vivo and in vitro efficacy against diabetes. Subsequently, these clinically approved drugs’ long-term side effects and metabolic resistance can enhance the search for novel small molecule-based α-glucosidase enzyme inhibitors to cure diabetes mellitus. In this present review, benzothiazole-based α-glucosidase inhibitors have been highlighted with their enriched structure-activity relationships containing the published research from (2013–2023), and we also discussed its in silico molecular docking mode of action. Most of the reported benzothiazole-based hybrids exhibited superior potency in vitro compared to approved drugs due to the vast probabilities of the chemical modifications and ligand-protein interactions with the benzothiazole ring. Moreover, significant hydrophobic target interactions, including π-π stacking, π-sulphur, π-cation, and π-anion, were observed during the entire study, which improved the inhibition target potency. The active target residues of α-glucosidase also developed sufficient binding pocket interaction with benzothiazole molecules and reduced the harmful effects. Hence, this study can provide a better understanding of the structural pattern with the in silico-based modification of benzothiazole scaffolds to improve current medication treatments for type-2 diabetes mellitus.