College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
Bioorg Med Chem Lett. 2010 Nov 15;20(22):6794-6. doi: 10.1016/j.bmcl.2010.08.114. Epub 2010 Sep 20.
A series of thiosemicarbazones 2(e-s) have been synthesized and studied their structure-activity relationship as melanogenesis inhibitor. Among them, (Z)-2-(naphthalen-1-ylmethylene)hydrazinecarbothioamide (2q, >100% inhibition at 10 μM, IC(50)=1.1 μM, ClogP=3.039) showed the strongest inhibitory activity. Regarding their structure-activity relationship, the hydrophobic substituents regardless the position on phenyl ring of benzaldehyde thiosemicarbazones enhance the inhibitory activity. Furthermore, the aromatic group of benzaldehydethiosemicarbazones can be replaced with sterically bulky cyclohexyl. Thus, hydrophobicity of the aryl or alkyl group on hydrazine of thiosemicarbazones is determinant factor for their inhibitory activity in melanogenesis rather than planarity.
一系列的缩硫酮 2(e-s) 已经被合成，并研究了它们作为黑色素生成抑制剂的构效关系。其中，（Z）-2-（萘-1-基亚甲基）肼甲硫酰胺（2q，在 10 μM 时抑制率>100%，IC（50）=1.1 μM，ClogP=3.039）表现出最强的抑制活性。关于它们的构效关系，苯甲醛缩硫酮中苯环上不论位置的疏水性取代基都增强了抑制活性。此外，苯甲醛缩硫酮的芳基可以用空间位阻较大的环己基取代。因此，缩硫酮中腙的芳基或烷基上的疏水性是决定其在黑色素生成中抑制活性的因素，而不是平面性。
