Synthesis and biological activities of ferulic acid derivatives

Three types of ferulic acid derivatives (feruloylaminoacid benzyl or methyl esters, feruloylaminoacids, and 4-0-[N-(carbobenzyloxy)-aminoacyl] ferulic acid) were synthesized by introduction of amino acids at different sites and their platelet aggregation (PA)-inhibitory, tyrosinase-inhibitory, angiotensin converting enzyme (ACE)-inhibitory, and superoxide dismutase (SOD)-like activities were evaluated. PA, one of the mechanisms involved in repair of blood vessel injury, is related to diseases such as thrombosis. Developing a compound capable of inhibiting PA may thus provide a therapeutic tool. From the results of study, particularly in the case of 4-0-[N-(carbobenzyloxy) aminoacyl] ferulic acid (amino acid components: isoleucine, proline), inhibition of collagen-induced aggregation was maintained of the same level as with ferulic acid, but stronger dissociation of ADP-induced aggregation was detected. In other words, these compounds may not only prevent thrombosis but also dissolve thrombi. Further, the compounds with stronger tyrosinase-inhibitory activity were found to scavenge superoxide as effectively as ferulic acid. Since they are also more hydrophobic, they may be particularly efficacious as cosmetic ingredients. Finally, feruloyl-Phe-Ala-Pro-OH had strong ACE inhibitory activity (IC50 = 1.5 microM) lacking in the case of ferulic acid itself.