Department of Molecular Chemistry and Biochemistry, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan.
Dalton Trans. 2022 Mar 22;51(12):4720-4727. doi: 10.1039/d1dt02868e.
Dicopper complexes Cu(μ-OH)(Ln) [ = 1 (1) and 2 (2)] with a novel phenanthrene amide-tether ligand conjugate (HL1) and the original -cresol-2,6-bis(amidecyclen) (HL2) were synthesized. A phenanthrene unit of 1 enhances the DNA-binding by 9-fold, enabling 1 to convert supercoiled plasmid DNA with HO to a linear one in a 9.3-fold higher yield than 2. 1 reacts with HO to form the μ-1,1-hydroperoxodicopper(II) complex 3 as the active species. The IC values of 1 against cancer cells of the lung and pancreas are 23.8 and 18.4 μM, respectively, 12-fold more toxic than the 284 and 241 μM of 2. Confocal microscopy, fluorescence-activated cell sorting, and caspase activity assays using HeLa cells revealed that 1 induces mitochondrial apoptosis. A DNA-targeting phenanthrene unit of 1 enhances the cancer-cell-selective toxicity mitochondrial apoptosis.
合成了具有新型菲酰胺键合配体共轭物（HL1）和原始间甲酚-2,6-双（酰胺环庚烷）（HL2）的二铜配合物[Cu(μ-OH)(Ln)]（ClO）[=1（1）和 2（2）]。1 中的菲单元使 DNA 结合增强了 9 倍，使 1 将超螺旋质粒 DNA 与 HO 转化为线性 DNA 的产率比 2 高 9.3 倍。1 与 HO 反应形成μ-1,1-过氧二铜（II）配合物 3 作为活性物质。1 对肺和胰腺癌细胞的 IC 值分别为 23.8 和 18.4 μM，毒性分别比 2 的 284 和 241 μM 高 12 倍。使用 HeLa 细胞的共聚焦显微镜、荧光激活细胞分选和半胱天冬酶活性测定表明，1 诱导线粒体细胞凋亡。1 的 DNA 靶向菲单元增强了癌细胞选择性毒性和线粒体细胞凋亡。
