Development of 1,2,3‐Triazoles as Dual Enzyme Inhibitors Targeting α‐Amylase and α‐Glucosidase for Type 2 Diabetes Intervention

ABSTRACT A series of fifteen 1,2,3‐triazole derivatives 6(a–o) were developed and evaluated for their inhibitory effects on carbohydrate‐hydrolyzing enzymes implicated in Type 2 diabetes management. The compounds were assessed through in silico studies (including molecular docking and ADME predictions) and in vitro assays such as α‐amylase, α‐glucosidase, and antioxidant activities. Notably, the compounds 6a , 6d , 6g , 6h , 6k , 6l , and 6n exhibited dual inhibition against both enzymes. Among them, compound 6a exhibited the most potent α‐glucosidase inhibition (IC 50 = 22.15 ± 0.75 µM), comparable to the reference drug acarbose (IC 50 = 21.07 ± 0.05 µM). Meanwhile, compound 6h demonstrated strong α‐amylase inhibition (IC 50 = 84.46 ± 1.14 µM) compared with standard acarbose (IC 50 = 87.62 ± 0.47 µM). Cytotoxicity studies of the most active compounds 6a and 6h indicated moderate cytotoxicity, with IC 50 values of 32.87 ± 1.2 µM and 32.42 ± 1.5 µM, respectively, suggesting a reasonable safety margin compatible with continued drug development. The DPPH assay revealed moderate to good activity for all compounds 6(a–o) , with IC 50 values ranging from 39.60 ± 0.15 to 99.45 ± 0.12 µM. These findings support the therapeutic potential of these compounds as antidiabetic agents.