Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential alpha-Glucosidase Inhibitors

alpha-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel alpha-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives (3a & SIM; 3v) were synthesized, and their alpha-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on alpha-glucosidase. Among them, compounds 3d, 3f, and 3i exhibited much better inhibitory activity with IC50 values of 49.89 +/- 1.16 mu M, 35.83 +/- 0.98 mu M, and 56.87 +/- 0.42 mu M, respectively, which were about 10 & SIM; 15 folds higher than acarbose (IC50 = 569.43 +/- 43.72 mu M). A kinetic mechanism study revealed that compounds 3d, 3f, and 3i inhibited the alpha-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and alpha-glucosidase.