Skin color is primarily produced by melanin, which is a crucial pigment that protects the
skin from UV-induced damage and prevents carcinogenesis. However, accumulated melanin in the
skin may cause hyperpigmentation and related disorders. Melanin synthesis comprises consecutive
oxidative reactions, and tyrosinase is the enzyme that catalyzes the rate-limiting process of melanogenesis.
In this study, tyrosinase-related protein 1 (TRP-1) and TRP-2 contributed to melanin formation.
N-(4-bromophenethyl) caffeamide ((E)-N-(4-bromophenethyl)-3-(3,4-dihydroxyphenyl)acrylamide;
K36H), a caffeic acid phenyl amide derivative, inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis
and tyrosinase activity in B16F0 cells. In addition, K36H reduced the protein expression of the phospho-cAMP response
element binding protein (p-CREB), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1.
Moreover, K36H promoted AKT and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, thereby inhibiting MITF
transcription activity. Thus, K36H attenuated α-MSH-induced cAMP pathways, contributing to hypopigmentation. The
results of a safety assay revealed that K36H did not exhibit cytotoxicity or irritate the skin or eyes. According to these results,
K36H may have the potential to be used as a whitening agent in the cosmetic and pharmaceutical industries.