A New Series of Salicylic Acid Derivatives as Non-saccharide alpha-Glucosidase Inhibitors and Antioxidants

摘要

In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide alpha-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of alpha-glucosidase inhibitory activity with IC50 values of 0.15 +/- 0.01, 0.0861 +/- 0.01 and 0.32 +/- 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with alpha-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of alpha-glucosidase by formation of an inhibitor-alpha-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and alpha-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide alpha-glucosidase inhibitors.