4-dodecylaminophenol and p-decylaminophenol

Melanin protects the skin against ultraviolet (UV) rays. It is produced in excess by UV radiation, which causes skin disorders and pigmentation. Retinoic acid (RA) decreases the levels of epidermal melanin by suppressing the expression of melanogenic enzymes including tyrosinase, which is the rate-limiting enzyme in melanin synthesis. However, RA shows inflammatory effects on the skin. In an effort to develop potent inhibitors of melanin synthesis, new aminophenol derivatives were synthesized based on structure-activity relationship studies of N-(4-hydroxyphenyl)retinamide (1), a derivative of RA. We investigated the inhibitory effects of a series of aminophenols on melanogenesis using B16 melanoma cells. p-Decylaminophenol (3) was the most potent agent examined, showing significant inhibition of B16 tyrosinase activities at concentrations less than what was required to achieve a similar level of inhibition by the well-known tyrosinase inhibitor, kojic acid. Compound 3 decreased melanin content and inhibited protein and mRNA expression for the tyrosinase-related protein-1 (TRP-1). It also inhibited the microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Compound 3 suppressed MEK/ERK signal pathways involved in the activation and expression of MITF. The data indicate that 3 inhibits TRP-1 expression by decreasing MITF expression through suppressing MEK/ERK signal pathways. This results in the reduction of melanin in B16 cells. Compound 3 might be an alternative to RA as a potent inhibitor of melanogenesis.

Topics: Aminophenols; Animals; Dose-Response Relationship, Drug; MAP Kinase Signaling System; Melanins; Mice; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured