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

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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 plantderived versions of UP302 inhibited mushroom tyrosinase with similar potencies. UP302 inhibited mushroom tvrosinase with K_i=0.3μM, in a competitive and reversible fashion. UP302 was 22 times more potent than Kojic acid in inhibiting murine tyrosinase, with IC_<50> values of 12 and 273μM respectively. Experiments on mouse melanoma cells B16-F1 and on human primary melanocytes demonstrated that UP302 inhibits melanin formation with IC_<50> values of 15 and 8μM respectively. Long-term treatment of cultured melanocytes with up to 62μM of UP302 revealed no detectable cytotoxicity. In a reconstructed skin model (MelanoDerm^<TM>) 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.
公益社団法人日本薬学会の論文
2008-09-01