Lee Chan Woo, Son Eun-Mi, Kim Han Sung, Xu Pan, Batmunkh Tuyagerel, Lee Burm-Jong, Koo Kyung Ah
R&D Center, AmorePacific Corporation, Kyounggi-do 449-729, Republic of Korea.
Bioorg Med Chem Lett. 2007 Oct 1;17(19):5462-4. doi: 10.1016/j.bmcl.2007.07.032. Epub 2007 Jul 25.
Three tyrosyl gallate derivatives (1-3) with variable hydroxyl substituent at the aromatic ring of tyrosol were synthesized and evaluated as potent inhibitors on tyrosinase activity and melanin formation in melan-a cells. Among three tyrosyl gallate derivatives, 4-hydroxyphenethyl 3,4,5-trihydroxybenote (1) (IC(50)=4.93 microM), 3-hydroxyphenethyl 3,4,5-trihydroxybenote (2) (IC(50)=15.21 microM), and 2-hydroxyphenethyl 3,4,5-trihydroxybenote (3) (IC(50)=14.50 microM) exhibited significant inhibitory effect on tyrosinase activity. Compound 1 was the most active compound, though it did not show the inhibitory effect on melanin formation in melan-a cells. However, compounds 2 (IC(50)=8.94 microM) and 3 (IC(50)=13.67 microM) significantly suppressed the cellular melanin formation without cytotoxicity. This study shows that the position of hydroxyl substituent at the aromatic ring of tyrosol plays an important role in the intracellular regulation of melanin formation in cell-based assay system.
合成了三种在酪醇芳环上具有可变羟基取代基的没食子酸酪氨酸酯衍生物（1-3），并评估了它们作为酪氨酸酶活性和黑素-a细胞中黑色素形成的有效抑制剂的作用。在三种没食子酸酪氨酸酯衍生物中，4-羟基苯乙基3,4,5-三羟基苯甲酸酯（1）（IC(50)=4.93 microM）、3-羟基苯乙基3,4,5-三羟基苯甲酸酯（2）（IC(50)=15.21 microM）和2-羟基苯乙基3,4,5-三羟基苯甲酸酯（3）（IC(50)=14.50 microM）对酪氨酸酶活性表现出显著的抑制作用。化合物1是活性最高的化合物，尽管它对黑素-a细胞中的黑色素形成没有抑制作用。然而，化合物2（IC(50)=8.94 microM）和3（IC(50)=13.67 microM）显著抑制细胞内黑色素的形成且无细胞毒性。这项研究表明，酪醇芳环上羟基取代基的位置在基于细胞的测定系统中对细胞内黑色素形成的调节起着重要作用。
