Rho Ho Sik, Baek Heung Soo, Ahn Soo Mi, Yoo Jae Won, Kim Duck Hee, Kim Han Gon
R & D Center, AmorePacific Corporation, 314-1, Bora-daong, Giheung-gu, Yongin-si, Kyounggi-do 449-729, Republic of Korea.
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1532-3. doi: 10.1016/j.bmcl.2008.12.106. Epub 2009 Jan 1.
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.
合成了六种含金刚烷部分的双酚化合物，并评估了它们对Melan - A细胞中酪氨酸酶活性和黑色素形成的强效抑制作用。在两种测定中，4 - 金刚烷基间苯二酚1的抑制活性与4 - 正丁基间苯二酚相似。然而，二羟基苯甲酰胺衍生物6a - e表现出不同的抑制模式。所有衍生物均显著抑制细胞黑色素形成，但无酪氨酸酶抑制活性。这些行为表明酰胺键的引入改变了二羟基与酪氨酸酶的结合模式。在衍生物中，与4 - 正丁基间苯二酚（IC(50)=21.64 microM）和对苯二酚（IC(50)=3.97 microM）相比，6d（3,4 - 二羟基化合物）和6e（2,3 - 二羟基化合物）表现出更强的抑制活性（分别为IC(50)=1.25 microM和0.73 microM）。该研究表明，芳环上二羟基取代基的位置对于细胞间黑色素形成的抑制很重要，并且酰胺键和金刚烷部分增强了抑制作用。
