title: 1-(2,4-dihydroxyphenyl)-3-(2,4-dimethoxy-3-methylphenyl)propane, a novel tyrosinase inhibitor with strong depigmenting effects.
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 K(i)=0.3 microM, 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 273 microM 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 8 microM respectively. Long-term treatment of cultured melanocytes with up to 62 microM of UP302 revealed no detectable cytotoxicity. In a reconstructed skin model (MelanoDerm) 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.
authors.affiliation: Unigen Pharmaceuticals, Inc., Lacey, WA 98516, USA. Anesterov@UnigenUSA.com
authors.forename: Alexandre
authors.initials: A
authors.lastname: Nesterov
authors.forename: Jifu
authors.initials: J
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Minter
authors.forename: Carmen
authors.initials: C
authors.lastname: Hertel
authors.forename: Wenwen
authors.initials: W
authors.lastname: Ma
authors.forename: Padmapriya
authors.initials: P
authors.lastname: Abeysinghe
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia