Design, synthesis, in vitro anti-α-glucosidase evaluations, and computational studies of new phthalimide-phenoxy-1, 2, 3-triazole-N-phenyl (or benzyl) acetamides as potential anti-diabetic agents

摘要: An important target in the treatment of type 2 diabetes is α-glucosidase. Inhibition of this enzyme led to delay in glucose absorption and decrease in postprandial hyperglycemia. A new series of phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides 11a–n were designed based on the reported potent α-glucosidase inhibitors. These compounds were synthesized and screened for their in vitro inhibitory activity against the latter enzyme. The majority of the evaluated compounds displayed high inhibition effects (IC50 values in the range of 45.26 ± 0.03–491.68 ± 0.11 µM) as compared to the positive control acarbose (IC50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC50 values of 45.26 ± 0.03 and 46.25 ± 0.89 µM. Kinetic analysis revealed that the compound 11j is a competitive inhibitor with a Ki of …