1-(2,4-Dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane, a Novel Tyrosinase Inhibitor with Strong Depigmenting Effects

Nesterov, Alexandre; Zhao, Jifu; Minter, David; Hertel, Carmen; Ma, Wenwen; Abeysinghe, Padmapriya; Hong, Mei; Jia, Qi

Publication

1-(2,4-Dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane, a Novel Tyrosinase Inhibitor with Strong Depigmenting Effects

Nesterov, Alexandre; Zhao, Jifu; Minter, David; Hertel, Carmen; Ma, Wenwen; Abeysinghe, Padmapriya; Hong, Mei; Jia, Qi

Publisher

The Pharmaceutical Society of Japan

Date

2008-09-01

Abstract

A series of diarylpropane compounds was isolated by screening a plant extract library for inhibitors of mushroom tyrosinase. The most potent compound, 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane (UP302: CAS# 869743-37-3), was found in the medicinal plant Dianella ensifolia. Synthetic and plant-derived versions of UP302 inhibited mushroom tyrosinase with similar potencies. UP302 inhibited mushroom tyrosinase with Ki=0.3 µM, in a competitive and reversible fashion. UP302 was 22 times more potent than Kojic acid in inhibiting murine tyrosinase, with IC50 values of 12 and 273 µM respectively. Experiments on mouse melanoma cells B16-F1 and on human primary melanocytes demonstrated that UP302 inhibits melanin formation with IC50 values of 15 and 8 µM respectively. Long-term treatment of cultured melanocytes with up to 62 µM of UP302 revealed no detectable cytotoxicity. In a reconstructed skin model (MelanoDermTM) topical application of 0.1% UP302 resulted in significant skin lightening and decrease of melanin production without effects on cell viability, melanocyte morphology or overall tissue histology. In conclusion, UP302 is a novel tyrosinase inhibitor that suppresses melanin production in both cultured melanocytes and reconstructed skin with high potency and without adverse side effects.