Biological evaluation and molecular docking of previously reported pyrazolo-thiazole derivatives as dual α-amylase and α-glucosidase inhibitors.

Abstract

Aim: Postprandial hyperglycemia is an important therapeutic target in type 2 diabetes mellitus. This study aimed to evaluate previously reported pyrazolo[3,4-d]thiazole derivatives as dual inhibitors of α-amylase and α-glucosidase.

Materials and methods: Compounds 5a-b, 6a-b and 7 were assessed using in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the reference inhibitor. The most active compounds were further evaluated for cytotoxicity against WI-38 normal human fibroblasts. Molecular docking was performed to explore binding modes within the active sites of the target enzymes.

Results: All tested compounds inhibited both enzymes in a dose-dependent manner. Compound 6b showed the strongest dual inhibitory activity, with IC₅₀ values of 0.24 μM against α-amylase and 1.34 μM against α-glucosidase, outperforming acarbose. Docking analysis supported these findings, showing favorable binding interactions of 6b within both enzyme active sites. Cytotoxicity testing indicated that the effective enzyme-inhibitory concentrations were markedly lower than the cytotoxic concentration in WI-38 cells.

Conclusion: Compound 6b represents a promising lead scaffold for further development of dual α-amylase/α-glucosidase inhibitors targeting postprandial hyperglycemia.