Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte-tyrosinase

Amides obtained by coupling caffeic acid, ferulic acid, p-hydroxycinnamoic acid, and analogues with substituted phenylalkylamines were evaluated as inhibitors of the human melanocyte-tyrosinase. The most active compounds induce a complete enzyme-inactivation at 100 μM. At the latter concentration, kojic acid, used as a reference, was inactive. Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin synthesis, catalyzing the transformation of tyrosine to l-dopaquinone. The aim of the present study was to study molecules able to inhibit melanin synthesis through inhibition of tyrosinase and their potential use in treating pigmentation-related disorders. We targeted amides obtained from coupling p-hydroxycinnamic acid derivatives with phenylalkylamines. The biological activity was evaluated on human melanocytes by an assay which measures tyrosine-catalyzed l-Dopa oxidation. The most active amides were: trans- N-caffeoyltyramine, N-dihydrocaffeoyltyramine, and trans- N-dihydro- p-hydroxycinnamoyltyramine which induce complete inhibition at 0.1 mM. At the latter concentration, kojic acid, which was used as the reference inhibitor, was inactive.