State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
Free Radic Biol Med. 2018 May 20;120:124-132. doi: 10.1016/j.freeradbiomed.2018.03.029. Epub 2018 Mar 16.
Altered redox status including higher levels of copper in cancer cells than in normal cells inspired many researchers to develop copper ionophores targeting this status. We have recently found that flavon-3-ol (3-HF) works as a potent Cu(II) ionophore by virtue of its keto-enol moiety. To further emphasize the significance of this moiety for developing Cu(II) ionophores, we herein designed a β-diketo analog of piperlongumine, PL-I, characterized by the presence of high proportion of the keto-enol form in dimethylsulfoxide and chloroform, and identified its keto-enol structure by NMR and theoretical calculations. Benefiting from deprotonation of its enolic hydroxyl group, this molecule is capable of facilitating the transport of Cu(II) through cellular membranes to disrupt redox homeostasis of human hepatoma HepG2 cells and trigger their death.
氧化还原状态的改变，包括癌细胞中铜的水平高于正常细胞，这激发了许多研究人员开发针对这种状态的铜载体。我们最近发现，黄酮-3-醇（3-HF）通过其酮-烯醇部分发挥有效的 Cu(II)载体作用。为了进一步强调该部分在开发 Cu(II)载体方面的重要性，我们设计了一种胡椒碱的β-二酮类似物 PL-I，其特点是在二甲基亚砜和氯仿中存在高比例的酮-烯醇形式，并通过 NMR 和理论计算确定了其酮-烯醇结构。受益于其烯醇羟基的去质子化，该分子能够促进 Cu(II)穿过细胞膜的运输，破坏人肝癌 HepG2 细胞的氧化还原稳态并引发其死亡。
