Melanins are pigments responsible for skin and hair fol- licles pigmentation in mammals. Melanin biosynthesis or melanogenesis occurs in specialized organelles, called melanosomes, through a cascade of enzymatic reactions

licles pigmentation in mammals. Melanin biosynthesis or melanogenesis occurs in specialized organelles, called melanosomes, through a cascade of enzymatic reactions using the amino acid tyrosine as the initial substrate. The first two steps in the biosynthetic pathway, hydroxylation of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) and oxidation of L-DOPA to dopaquinone, are catalyzed by tyrosinase, a copper-containing, membrane-bound glycoprotein that is the rate limiting enzyme of the melanin biosynthetic pathway. Abnormal melanin production such as observed in melasma, freckles, lentigo senilis, and other forms of melanin hyperpigmentation can be a serious aesthetic problem often causing emotional disturbance. Taking into account the key role of tyrosinase in melanin production, many tyrosinase inhibitors have found application in cosmetics and pharmaceutical products. However, most of them are unsatisfactory due to the weak cosmetic/clinical effects and/or to the various safety concerns. Thus hydroquinone reported to induce inhibitory activity against tyrosinase is considered to be highly cytotoxic and mutagenic to mammals cells. Leaving a door opened for the discovery of new tyrosinase inhibitors many efforts have been made in the search for safe and efficient tyrosinase inhibitors. Phenolic compounds such as cinnamic acid and its derivatives (caffeic acid, ferulic acid), have been reported to act as tyrosinase inhibitors. In a recent study Okombi et al. investigated the effect of amides derived from coupling of caffeic acid, ferulic acid and derivatives with phenylalkylamines (tyramine, dopamine) as inhibitors of tyrosinase. They demonstrated the potency of some derivatives such as the Ncaffeoyltyramine but they did not investigate the effect of other derivatives of p-coumaric acid, cinnamic acid obtained by coupling with other phenylalkylamine or phenylmethylamine derivatives. Besides due to high attrition rate of the previously developed tyrosinase inhibitors when moving from in vitro to in vivo studies, it appears important to find out new tyrosinase inhibitory molecules. On this basis, we synthetized N-(phenylalkyl)cinnamides derived from the coupling of cinnamic acid or its derivatives with phenylalkylamines and evaluated their potential to inhibit tyrosinase activity.