Synthesis and Biological Evaluation of Piperic Acid Amides as Free Radical Scavengers and α-Glucosidase Inhibitors

A series of piperic acid amides (4-24, 29, 30) were synthesized and their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and a-glucosidase inhibitory activities were evaluated. Among the synthesized compounds, the amides 11, 13 and 15, which contain o-methoxyphenol, catechol or 5-hydroxyindole moieties, showed potent DPPH free radical scavenging activity (11: EC50 140,mu m; 13: EC50 28 mu m; 15: EC50 20 mu m). The amides 10, 18 and 23 showed higher inhibitory activity of a-glucosidase (10: IC50 21 mu m; 18: IC50 21 mu m; 23: IC50 12 mu m). These data suggest that the hydrophobicity of the conjugated amines is an important determinant of alpha-glucosidase inhibitory activity. In addition, the amides 13 and 15 showed both potent DPPH free radical scavenging activity and a-glucosidase inhibitory activity (13: IC50 46 mu m; 15: IC50 46 mu m). This is the first report identifying the DPPH free radical scavenging and a-glucosidase inhibitory activities of piperic acid amides and suggests that these amides may serve as lead compounds for the development of novel a-glucosidase inhibitors with antioxidant activity.