Synthesis, discovery and mechanism of 2,6-dimethoxy-N-(4-methoxyphenyl)benzamide as potent depigmenting agent in the skin

被引:20
作者
Choi, Sang Yoon
Hwang, Jae Sung
Kim, Sanghee
Kim, Sun Yeou [1 ]
机构
[1] Kyung Hee Univ, Grad Sch, EW Med Sci, Suwon, South Korea
[2] Seoul Natl Univ, Coll Pharm, Seoul, South Korea
[3] Amore Pacific R&D, Skin Res Inst, Yongin, South Korea
[4] Korea Food Res Inst, Songnam, South Korea
关键词
melanin; depigment agent; biaryl amide; dopachrome tautomerase; skin;
D O I
10.1016/j.bbrc.2006.07.206
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this study, a new skin-depigmenting agent, 2,6-dimethoxy-N-(4-methoxyphenyl)benzamide (DMPB), was synthesized using a combination of benzoic acid and aniline. DMPB exhibited significant depigmentation ability on the UV B-induced hyperpigmentation of the brown guinea pig skin. In addition, the 100 ppm treatment with this compound had a 30% inhibitory effect on melanin pigment generation in the melan-a cell line without significant cell toxicity. To search for relationship with the depigmentation, the effects of DMPB on the tyrosinase and dopachrome tautomerase were evaluated. DMPB had no effect on tyrosinase. However, it accelerated dopachrome transformation into 5,6-dihydroxyindole-2-carboxylic acid (DHICA) in the presence of dopachrome tautormerase. In addition, intracellular level of dopachrome tautomerase in melan-a cells was increased by treatment of DMPB. These results suggest that the pigment-lightening effects of DMPB might be due to biased production of DHICA-eumelanin induced by dopachrome tautormerase activation. (c) 2006 Published by Elsevier Inc.
引用
收藏
页码:39 / 49
页数:11
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