Synthesis, discovery and mechanism of 2,6-dimethoxy-N-(4-methoxyphenyl)benzamide as potent depigmenting agent in the skin.
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 100ppm 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.
Choi
Sang Yoon
SY
Korea Food Research Institute, Songnam, Republic of Korea.
Hwang
Jae Sung
JS
Kim
Sanghee
S
Kim
Sun Yeou
SY
D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D000840:Anisoles / Q000138:chemical synthesis* / Q000737:chemistry*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D019817:Benzoic Acid / Q000737:chemistry; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000737:chemistry; D019746:Intramolecular Oxidoreductases / Q000737:chemistry; D008956:Models, Chemical; D014442:Monophenol Monooxygenase / Q000737:chemistry; D012867:Skin / Q000187:drug effects*
C514739:2,6-dimethoxy-N-(4-methoxyphenyl)benzamide; D000814:Aniline Compounds; D000840:Anisoles; D001549:Benzamides; D007211:Indoles; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; D019817:Benzoic Acid; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C023650:aniline