Phenylethylamide and Phenylmethylamide Derivatives as New Tyrosinase Inhibitors

Increased production and accumulation of melanin lead to hyperpigmentation disorders. Several inhibitors of tyrosinase, the key enzyme in melanin synthesis have been developed but exhibited lack of efficiency or some adverse side effects. Therefore, it appears very important to find new agents that will be able to promote inhibition of tyrosinase and pigmentation. In this study, some phenylalkylcinnamide molecules were synthesized and evaluated for their ability to act as tyrosinase inhibitors. Compounds 2(IC50＝0.03mM)and 12(IC50＝0.028mM)showed strong tyrosinase inhibitory potential comparable to standard hydroquinone(IC50＝0.037mM). Taken together, compounds 2 and 12 can be considered as good candidates for further investigations to evaluate their effect on the inhibition of melanin synthesis and skin pigmentation. Melanins are pigments responsible for skin and hair follicles 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.