Tyrosinase inhibitory effects and antioxidative activities of novel cinnamoyl amides with amino acid ester moiety

Nine cinnamoyl amides with amino acid ester (CAAE) moiety were synthesized by the conjugation of the corresponding cinnamic acids (cinnamic acid, 4-hydroxy cinnamic acid, ferulic acid and caffeic acid) with amino acid esters, and their inhibitory effects on the activities of mushroom tyrosinase were investigated, using l-3,4-dihydroxyl-phenylalanine (l-DOPA) as the substrate. Among these CAAE amides, ethyl N-[3-(4-hydroxy-3-methoxyphenyl)-1-oxo-2-propen-1-yl]-l-phenylalaninate (b4) showed the strongest inhibitory activity; the IC50 was 0.18 μM. The IC50 values, inhibition types, inhibition mechanisms and kinetics of all these CAAE amides were evaluated. A structure–activity relationship (SAR) study found that the inhibitory effects were potentiated with the increasing length of hydrocarbon chains at the amino acid esters and also influenced by the substituents at the styrene groups. Furthermore, the hydroxyl radical scavenging and anti-lipid peroxidation activities of four CAAE derivatives were also investigated. Among these compounds, b3 (ethyl N-[3-(3,4-dihydroxyphenyl)-1-oxo-2-propen-1-yl]-l-phenylalaninate) and b4 exhibited potential antioxidant activities.