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.

中文翻译：

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1-（2,4-二羟基苯基）-3-（2,4-二甲氧基-3-甲基苯基）丙烷，一种新型的酪氨酸酶抑制剂，具有很强的脱色效果。

通过筛选植物提取物文库中蘑菇酪氨酸酶抑制剂，分离出一系列二芳基丙烷化合物。最有效的化合物1-（2,4-二羟基苯基）-3-（2,4-二甲氧基-3-甲基苯基）丙烷（UP302：CAS＃869743-37-3）被发现在药用植物Dianella ensifolia中。UP302的合成和植物来源版本抑制蘑菇酪氨酸酶的功效相似。UP302以竞争和可逆的方式抑制K（i）= 0.3 microM的蘑菇酪氨酸酶。UP302在抑制鼠酪氨酸酶方面比曲酸高22倍，IC（50）值分别为12和273 microM。对小鼠黑色素瘤细胞B16-F1和人原代黑色素细胞的实验表明，UP302抑制黑色素形成，其IC（50）值分别为15和8 microM。用高达62 microM的UP302长期处理培养的黑素细胞，未发现可检测的细胞毒性。在重建的皮肤模型（MelanoDerm）中，局部应用0.1％UP302可使皮肤显着增白，黑色素生成减少，而不会影响细胞活力，黑色素细胞形态或整体组织组织学。总之，UP302是一种新型的酪氨酸酶抑制剂，可高效抑制培养的黑素细胞和重建皮肤中黑色素的产生，且无不良副作用。