N-Hydroxycinnamoyl amides of fluorinated amino acids: Synthesis, anti-tyrosinase and DPPH scavenging activities

• Published in: Journal of fluorine chemistry 2013-12, Vol.156, p.203-208
• Main Authors: Chochkova, Maya, Stoykova, Boyka, Ivanova, Galya, Ranz, Andreas, Guo, Xinghua, Lankmayr, Ernst, Milkova, Tsenka
• Format: Article
• Language: English
• Subjects: Amides; Amino acids; Anti-tyrosinase activity; Antioxidants; DPPH; Fluorinated amino acids; Fluorination; Fluorine; Mushroom tyrosinase; N-hydroxycinnamoylamides; Radicals; Scavenging
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2013.09.013

N-hydroxycinnamoylamides containing fluorinated amino acids were prepared and their anti-tyrosinase and DPPH scavenging activities were evaluated. •Eight N-hydroxycinnamoylamides of fluorinated amino acids have been synthesized, among them five are new.•We evaluated their antioxidative activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test.•Among the tested amides, N-sinapoyl-3-fluorotyrosine methyl ester (5) exhibited the highest radical-scavenging activity.•SA-Trp(6-F)-OMe (4) inhibited the most significantly the formation of dopachrome in anti-tyrosinase assay. A series of N-hydroxycinnamoyl amides of fluorinated amino acids were synthesized. Their antioxidant activity was determined using the rapid DPPH test and the activity was compared to that of non-fluorinated analogs and standard antioxidants. Results on the antiradical properties obtained by Nenadis’ method, indicate that fluorine slightly increased the radical scavenging activity of three of the studied amides. Among the tested compounds, sinapic acid (the standard) was the most potent one according to the DPPH radical scavenging assay, followed by N-sinapoyl-3-fluorotyrosine methyl ester. The amides tested by DPPH–HPLC method possessed similar radical scavenging activity as compared to the used eugenol and isoeugenol standards. Moreover, the inhibitory activities of N-hydroxycinnamoyl amides of fluorinated amino acids on mushroom tyrosinase using l-tyrosine as a substrate, were evaluated in vitro. The results showed that SA-Trp(6-F)-OMe (4) was the most effective tyrosinase inhibitor among the tested amides. Two of the fluorinated amides (SA-Trp(6-F)-OMe (4) and SA-Tyr(3-F)-OMe (5)) revealed no significant difference in their anti-tyrosinase activity in comparison to p-coumaric acid (control), but lower one than hydroquinone used as standard.