School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China.
Eur J Med Chem. 2018 Oct 5;158:853-862. doi: 10.1016/j.ejmech.2018.09.034. Epub 2018 Sep 15.
Copper(II) complexes efficiently catalyze hydrogen peroxide to generate reactive oxygen species (ROS), which is the major reason for its significant anti-tumor activity. We synthesized three Cu(II) piperidylthiosemicarbazone complexes and examined their structures by X-ray single crystal diffraction. These Cu(II) complexes have significant apoptosis-promoting activity at nanomolar concentrations. The antitumor activity of these Cu(II) complexes is increased by more than 40-fold relative to that of the ligand. The binding experiment results demonstrated that the Cu(II) complexes interact with DNA with moderate binding affinity by in situ intercalation. Gel electrophoresis analysis indicated that DNA is degraded when the copper complex catalyzes hydrogen peroxide to produce reactive oxygen species (ROS). Apoptosis mechanism results showed that excessive ROS leads to mitochondrial membrane potential dissipation and promote the release of apoptotic factors from mitochondria.
铜（II）配合物能有效地催化过氧化氢生成活性氧物种（ROS），这是其具有显著抗肿瘤活性的主要原因。我们合成了三种铜（II）哌啶基硫代缩氨基脲配合物，并通过 X 射线单晶衍射对其结构进行了研究。这些铜（II）配合物在纳摩尔浓度下具有显著的促凋亡活性。与配体相比，这些铜（II）配合物的抗肿瘤活性提高了 40 多倍。结合实验结果表明，铜（II）配合物通过原位嵌入与 DNA 具有中等结合亲和力。凝胶电泳分析表明，当铜配合物催化过氧化氢产生活性氧物种（ROS）时，DNA 会被降解。凋亡机制结果表明，过量的 ROS 导致线粒体膜电位耗散，并促进凋亡因子从线粒体中释放。
