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

• Published in: Chemical & pharmaceutical bulletin Vol. 63; no. 5; pp. 326 - 333
• Main Authors: Takao, Koichi, Miyashiro, Takaki, Sugita, Yoshiaki
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.05.2015; Pharmaceutical Soc Japan
• Subjects: alpha-Glucosidases - metabolism; antioxidant; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Fatty Acids, Unsaturated - chemistry; Free Radical Scavengers - chemical synthesis; Glycoside Hydrolase Inhibitors - chemical synthesis; Glycoside Hydrolase Inhibitors - pharmacology; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; piperine; Science & Technology; structure–activity relationship; α-glucosidase inhibitor; ANTIOXIDANT ACTIVITY; antioxidant; OXIDATIVE STRESS; alpha-glucosidase inhibitor; BLACK PEPPER; piperine; SEROTONIN; structure-activity relationship; DERIVATIVES
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c14-00874

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