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

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 (IC₅₀ = 22.15 ± 0.75 µM), comparable to the reference drug acarbose (IC₅₀ = 21.07 ± 0.05 µM). Meanwhile, compound 6h demonstrated strong α-amylase inhibition (IC₅₀ = 84.46 ± 1.14 µM) compared with standard acarbose (IC₅₀ = 87.62 ± 0.47 µM). Cytotoxicity studies of the most active compounds 6a and 6h indicated moderate cytotoxicity, with IC₅₀ 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 IC₅₀ 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.