College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):886-9. doi: 10.1016/j.bmcl.2011.12.035. Epub 2011 Dec 13.
2-(Naphthalen-1-ylmethylene)hydrazinecarbothioamide (14, IC(50)=1.1μM) was discovered as a highly potent inhibitor of melanogenesis. To define the role of hydrogens (at N1 and N3) and sulfur in 14, a series of analogs 15a-p were synthesized and evaluated for anti-melanogenic activity using melanoma B16 cells under the stimulus of α-MSH. It was observed that replacement of either of these hydrogens at N1 or N3 by substituents increases the activity significantly. Conversely, concomitant substitutions decrease the inhibitory potency. In addition, the presence of sulfur in thiosemicarbazone is essential for the activity.
2-(萘-1-亚甲基)肼二硫代酰胺（14，IC（50）=1.1μM）被发现是一种非常有效的黑色素生成抑制剂。为了确定氢（在 N1 和 N3 上）和硫在 14 中的作用，合成了一系列类似物 15a-p，并在α-MSH 的刺激下用黑素瘤 B16 细胞评估了它们的抗黑色素生成活性。观察到，用取代基取代 N1 或 N3 上的这些氢中的任何一个都会显著提高活性。相反，同时取代会降低抑制效力。此外，硫代腙中硫的存在对于活性是必需的。
