Design, synthesis, biological evaluation, and docking study of new triazole-phenylacetamide derivatives as α-glucosidase inhibitors.

To discover potent α-glucosidase inhibitors, a class of novel triazole-phenylacetamide derivatives (5a-5p) were designed, prepared, and tested for their α-glucosidase inhibitory effects. All tested compounds (5a-5p) displayed a strong α-glucosidase inhibitory activity (IC = 6.69 ± 0.18-113.65 ± 2.94 μM) in comparison with the positive control acarbose (IC = 723.06 ± 11.26 μM). Thereinto, 5g (IC = 6.69 ± 0.18 μM) showed the best anti-α-glucosidase activity and behaved as a mixed-type inhibitor with the value of K and K to be 1.65 μM and 4.54 μM, respectively. Besides, fluorescence quenching experiment, three-dimensional fluorescence spectra assay, circular dichroism analysis, and molecular docking studies indicated that 5g may inhibit α-glucosidase activity by binding with its active site as well as changing the secondary structure of α-glucosidase. Combined with the inhibition effect on the rise of postprandial blood glucose level and low cytotoxicity of 5g, it could be concluded that these title compounds may play a role as lead compounds to develop novel α-glucosidase inhibitors.