Mixed-ligand copper(II) Schiff base complexes: the role of the co-ligand in DNA binding, DNA cleavage, protein binding and cytotoxicity
Mixed-ligand copper(II) Schiff base complexes: the role of the co-ligand in DNA binding, DNA cleavage, protein binding and cytotoxicity
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混合配体铜 (II) 席夫碱配合物：辅助配体在 DNA 结合、DNA 切割、蛋白质结合和细胞毒性中的作用
DOI：
10.1039/c6dt00461j
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发表时间：
2016
影响因子：
4
通讯作者：
Xu Jing-Yuan
中科院分区：
文献类型：
--
作者：
Lian Wen-Jing;Wang Xin-Tian;Xie Cheng-Zhi;Tian He;Song Xue-Qing;Pan He-Ting;Qiao Xin;Xu Jing-Yuan
合成了[Cu(L)(OAc)]·H2O(1)、[Cu(HL)(C2O4)(EtOH)]·EtOH(2)、[Cu(L)(Bza)](3)和[Cu（L)（Sal)] （4) （HL = 1-（（2-羟丙基）氨基）亚氨基）甲基）萘-2-醇）、Bza =苯甲酸、Sal =水杨酸）4种新型单核希夫碱铜（II）配合物，并用x射线晶体学、元素分析和红外光谱对其进行了表征。单晶衍射分析表明，所有配合物均为单核分子，其中希夫碱配体具有不同的配位模式和构象。分子间和分子内的N-H⋯O和O - h⋯O氢键相互作用将这些分子连接成多维网络。它们与小牛胸腺DNA （CT-DNA）的相互作用通过紫外可见光谱和荧光光谱以及粘度测量进行了研究。4个复合物的Kapp值均为105，表明复合物与DNA之间具有中等的插入结合模式。电泳结果表明，这些复合物均通过氧化途径在H2O2存在下诱导pUC19质粒DNA双链断裂。此外，配合物对人血清白蛋白（HSA）的荧光光谱分析表明，配合物对HSA的猝灭机制是一个静态的过程。此外，通过比色细胞增殖实验和克隆实验评估了四种复合物对人宫颈癌（HeLa）和肝癌（HepG-2）细胞的抗增殖活性，结果表明四种复合物对癌细胞的细胞毒性均有所提高。令人鼓舞的是，以水杨酸为辅助配体的配合物4显示出更强的抗癌活性，这表明希夫碱配合物与非甾体抗炎药的协同作用可能参与了细胞杀伤过程。本文还讨论了铜（II）希夫碱混合配体配合物的生物学特性以及醋酸辅助配体如何调控这些特性。
Four novel mononuclear Schiff base copper(II) complexes, namely, [Cu(L)(OAc)]·H2O (1), [Cu(HL)(C2O4)(EtOH)]·EtOH (2), [Cu(L)(Bza)] (3) and [Cu(L)(Sal)] (4) (HL = 1-(((2-((2-hydroxypropyl)amino)ethyl)imino)methyl)naphthalene-2-ol), Bza = benzoic acid, Sal = salicylic acid), were synthesized and characterized by X-ray crystallography, elemental analysis and infrared spectroscopy. Single-crystal diffraction analysis revealed that all the complexes were mononuclear molecules, in which the Schiff base ligand exhibited different coordination modes and conformations. The N–H⋯O and O–H⋯O inter- and intramolecular hydrogen bonding interactions linked these molecules into multidimensional networks. Their interactions with calf thymus DNA (CT-DNA) were investigated by UV-visible and fluorescence spectrometry, as well as by viscosity measurements. The magnitude of the Kapp values of the four complexes was 105, indicating a moderate intercalative binding mode between the complexes and DNA. Electrophoresis results showed that all these complexes induced double strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. In addition, the fluorescence spectrum of human serum albumin (HSA) with the complexes suggested that the quenching mechanism of HSA by the complexes was a static process. Moreover, the antiproliferative activity of the four complexes against HeLa (human cervical carcinoma) and HepG-2 (human liver hepatocellular carcinoma) cells evaluated by colorimetric cell proliferation assay and clonogenic assay revealed that all four complexes had improved cytotoxicity against cancer cells. Inspiringly, complex 4, with salicylic acid as the auxiliary ligand, displayed a stronger anticancer activity, suggesting that a synergistic effect of the Schiff base complex and the nonsteroidal anti-inflammatory drug may be involved in the cell killing process. The biological features of mixed-ligand copper(II) Schiff base complexes and how acetic auxiliary ligands manipulate these features are also discussed.