Merck

Inhibitory effects of p-alkylaminophenol on melanogenesis.

Bioorganic & medicinal chemistry (2014-08-16)
Noriko Takahashi, Masahiko Imai, Yu Komori
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, ≥99.6%, ReagentPlus®
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
3,4-Dihydroxy-L-phenylalanine, ≥98% (TLC)
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Levodopa, European Pharmacopoeia (EP) Reference Standard
USP
L-Tyrosine, United States Pharmacopeia (USP) Reference Standard
USP
Levodopa, United States Pharmacopeia (USP) Reference Standard
Supelco
Levodopa, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Tyrosine, certified reference material, TraceCERT®
Sigma-Aldrich
L-Tyrosine, FG
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
L-Tyrosine, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Tyrosine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 99.0-101.0%