Synthetic strategies, biological and computational screening of thiadiazole bearing benzothiazole derivatives as prospective anti-diabetic agents

Abstract

This study explores the synthesis and biological evaluation of novel thiadiazole bearing benzothiazole derivatives as potential dual inhibitors of α-amylase and α-glucosidase enzymes critical in carbohydrate metabolism. Inhibiting these enzymes offers a promising therapeutic strategy for managing postprandial hyperglycemia in type 2 diabetes. A series of imidazopyridine-derived thiadiazole bearing benzothiazole derivatives (1–18) were synthesized and were also structurally elucidated through ¹H NMR, ¹³C NMR and HREI-MS analysis. These derivatives were subjected to in vitro enzyme inhibition assays, revealing significant inhibitory activities with IC₅₀ values ranging from 12.20 ± 2.70 to 46.90 ± 6.60 µM for α-amylase, and from 12.50 ± 1.90 to 48.60 ± 6.80 µM for α-glucosidase. These results were compared with the standard drug Acarbose, which exhibited IC₅₀ values of 32.40 ± 2.30 µM for α-amylase and 35.70 ± 2.70 µM for α-glucosidase. Notably, compounds 13, 10, 9, 7 and 3 displayed the most potent inhibition against both α-amylase and α-glucosidase. Additionally, molecular docking studies were conducted to predict binding interactions between the synthesized derivatives and the active sites of α-amylase and α-glucosidase. The in-silico results corroborated the in vitro findings, showing strong binding affinities and interaction patterns, suggesting these derivatives as promising candidates for further development in antidiabetic therapy.