Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, Republic of Korea.
Eur J Med Chem. 2012 Nov;57:383-90. doi: 10.1016/j.ejmech.2012.09.026. Epub 2012 Sep 23.
We attempted to design and synthesize (E)-N-substituted benzylidene-hydroxy or methoxy-aniline derivatives and to evaluate their inhibitory effect on tyrosinase activity and anti-melanogenesis activity in murine B16F10 melanoma cells. Derivatives with a 4-methoxy- or 4-hydroxy-anilino group exerted more potent inhibition against mushroom tyrosinase than those with a 2-hydroxyanilino group. (E)-4-((4-Hydroxyphenylimino)methyl)benzene-1,2-diol exhibited the most potent and non-competitive inhibition on mushroom tyrosinase showing an IC(50) of 17.22 ± 0.38 μM and being more effective than kojic acid (51.11 ± 1.42 μM). This compound decreased melanin production stimulated by the alpha-melanocyte-stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent manner. Therefore, we propose (E)-4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol as a new candidate of potent tyrosinase inhibitors that could be used as therapeutic agent with safe skin-whitening efficiency.
我们试图设计和合成（E）-N-取代的苄叉基-羟或甲氧基苯胺衍生物，并评估它们对蘑菇酪氨酸酶活性和鼠 B16F10 黑素瘤细胞中黑色素生成活性的抑制作用。具有 4-甲氧基-或 4-羟基苯胺基的衍生物对蘑菇酪氨酸酶的抑制作用强于具有 2-羟基苯胺基的衍生物。（E）-4-（（4-羟基苯基亚氨基）甲基）-1,2-苯二酚对蘑菇酪氨酸酶表现出最有效和非竞争性抑制作用，IC50 为 17.22 ± 0.38 μM，比曲酸（51.11 ± 1.42 μM）更有效。该化合物可减少α-黑色素细胞刺激激素刺激的黑色素生成，并以剂量依赖的方式抑制鼠酪氨酸酶活性。因此，我们提出（E）-4-（（4-羟基苯基亚氨基）甲基）-1,2-苯二酚作为一种潜在的酪氨酸酶抑制剂的新候选物，可作为具有安全美白功效的治疗剂使用。
