Studies on depigmenting activities of dihydroxyl benzamide derivatives containing adamantane moiety.
Six diphenolic compounds containing adamantane moiety were synthesized and evaluated as potent inhibitors on tyrosinase activity and melanin formation in Melan-A cells. The inhibitory activity of 4-adamantyl resorcinol 1 was similar to that of 4-n-butyl resorcinol in both assays. However, dihydroxyl benzamide derivatives 6a-e showed different inhibitory patterns. All derivatives significantly suppressed the cellular melanin formation without tyrosinase inhibitory activities. These behaviors indicated that the introduction of amide bond changes the binding mode of dihydroxyl groups to tyrosinase. Among derivatives, 6d (3,4-dihydroxyl compound) and 6e (2,3-dihydroxyl compound) showed stronger inhibitory activities (IC(50)=1.25 microM and 0.73 microM, respectively) as compared to 4-n-butyl resorcinol (IC(50)=21.64 microM) and hydroquinone (IC(50)=3.97 microM). This study showed that the position of dihydroxyl substituent at aromatic ring is important for the intercellular inhibition of melanin formation, and also amide linkage and adamantane moiety enhance the inhibition.
Rho
Ho Sik
HS
R & D Center, AmorePacific Corporation, 314-1, Bora-daong, Giheung-gu, Yongin-si, Kyounggi-do 449-729, Republic of Korea.
Baek
Heung Soo
HS
Ahn
Soo Mi
SM
Yoo
Jae Won
JW
Kim
Duck Hee
DH
Kim
Han Gon
HG
D000218:Adamantane / Q000138:chemical synthesis* / Q000494:pharmacology; D000363:Agaricales; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D010860:Pigments, Biological / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
D001549:Benzamides; D008543:Melanins; D010860:Pigments, Biological; D014442:Monophenol Monooxygenase; D000218:Adamantane