Imidazol-1,2,3-triazole Derivatives as Novel and Potent Scaffolds of α-Glucosidase Inhibitors: Synthesis and Biological Evaluations

Abstract

A treatment for type 2 diabetes mellitus (T2DM) that has been approved is the inhibition of α-glucosidase. Using a simple and straightforward three-step synthetic route that utilized a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry approach in the last step, a new series of substituted 1H-imidazol-1H-1,2,3-triazoles, specifically 5a–5j, were synthesized in an effort to create new anti-α-glucosidase agents. ¹H and ¹³C NMR spectroscopy and mass spectrometry were used to characterize these motifs in great detail. The positive control in this investigation was acarbose, which had an IC₅₀ value of 750.0 µM. The 1H-imidazol-1H-1,2,3-triazoles that were replaced showed inhibitory potencies several times stronger than those of conventional medicines, with IC₅₀ values ranging from 14.89 to 311.20 μM. In particular, compounds containing fluorine groups as aryl substitutions exhibited anti-α-glucosidase activity with an IC₅₀ value of 14.89 μM (5f = 4-CF₃), which was 53 times stronger than the positive control acarbose, while compounds carrying the 2,4-(F)₂ motif had an IC₅₀ value of 29.50 μM, which was 25 times stronger.