Inhibitory effect of N-adamantyl-3,4-dihydroxybenzamide on melanogenesis in melan-a cells and brown guinea pigs.
To find novel depigmenting agents, a new synthetic compound, N-adamantyl-3,4-dihydroxybenzamide (NADB) was produced and the effects on melanogenesis were investigated. Our results showed that NADB reduced melanin synthesis in a dose-dependent manner in melan-a cells. Tyrosinase activity was also reduced by NADB treatment in melan-a cells. However, NADB did not inhibit tyrosinase activity directly in a cell-free system. Treatment of melan-a cells with NADB caused a marked decrease in protein and mRNA levels of tyrosinase along with tyrosinase-related protein 1 and dopachrome tautomerase. To determine whether NADB reduces skin pigmentation, the dorsal skin of brown guinea pigs was shaved and irradiated with UV for 3 weeks using a solar simulator. Then NADB (2 or 1% in propylene glycol:ethanol:water = 5:3:2) was applied topically twice daily for 4 weeks. Visual inspection and Fontana-Masson staining both demonstrated that NADB resulted in lower skin pigmentation and total epidermal melanin in comparison to vehicle-treated areas. These findings suggest that NADB is useful in the treatment of hyperpigmentation.
Rho
Ho Sik
HS
R & D Center, AmorePacific Corporation, Giheung-gu, Yongin, Korea.
Ahn
Soo Mi
SM
Hwang
Jae Sung
JS
D000218:Adamantane / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006168:Guinea Pigs; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010859:Pigmentation Disorders / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects / Q000528:radiation effects
D008543:Melanins; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D000218:Adamantane