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1,10-菲咯啉与三齿酚盐/吡啶基/(苯)咪唑基席夫碱配体形成的混合配体铜(II)配合物:共价与非共价DNA结合、DNA裂解及细胞毒性

Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: covalent vs non-covalent DNA binding, DNA cleavage and cytotoxicity.

作者信息

Rajarajeswari Chandrasekaran, Ganeshpandian Mani, Palaniandavar Mallayan, Riyasdeen Anvarbatcha, Akbarsha Mohammad Abdulkadher

机构信息

School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India.

Department of Chemistry, Central University of Tamil Nadu, Thiruvarur 610004, Tamil Nadu, India.

出版信息

J Inorg Biochem. 2014 Nov;140:255-68. doi: 10.1016/j.jinorgbio.2014.07.016. Epub 2014 Aug 1.

DOI:10.1016/j.jinorgbio.2014.07.016
PMID:25199844
Abstract

A series of copper(II) complexes of the types Cu(L)(phen) 1-2, where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1H-benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1H-benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and Cu(L)(phen)23-6, where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1H-benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1H-benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1H-benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1-6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a-2a and [Cu(3N)Cl2] 3a-6a. On prolonged incubation, all the complexes 1-6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a-6a, and have the potential to act as efficient cytotoxic drugs.

摘要

一系列通式为Cu(L)(phen) 1 - 2的铜(II)配合物已被分离出来并用不同光谱技术进行了表征,其中HL是一种具有两个氮供体原子和一个氧供体原子(2NO)的三齿配体,如2-(2-(1H - 苯并咪唑 - 2 - 基)乙基亚氨基甲基)苯酚(HL1)和2-(2-(1H - 苯并咪唑 - 2 - 基)乙基 - 亚氨基)甲基)-4 - 甲基苯酚(HL2),phen是1,10 - 菲咯啉;还有通式为Cu(L)(phen)2 3 - 6的配合物,其中L是一种具有三个氮供体原子(3N)的三齿配体,如(2 - 吡啶 - 2 - 基乙基)吡啶 - 2 - 基亚甲基胺(L3)、2-(1H - 苯并咪唑 - 2 - 基)乙基)-吡啶 - 2 - 基亚甲基胺(L4)、2-(1H - 苯并咪唑 - 2 - 基)乙基)(1H - 咪唑 - 2 - 基亚甲基)-胺(L5)和2-(1H - 苯并咪唑 - 2 - 基)乙基)(4,4a - 二氢喹啉 - 2 - 基亚甲基)胺(L6)。在单晶X射线结构中,1具有扭曲的三角双锥的方锥(SPDTBP)几何构型,而3和4具有扭曲的方锥的三角双锥(TBDSP)几何构型。紫外 - 可见光谱和荧光光谱研究表明,配合物1 - 6与小牛胸腺DNA的非共价结合比相应的共价结合的氯配合物[Cu(2NO)Cl] 1a - 2a和[Cu(3N)Cl2] 3a - 6a更强。长时间孵育后,所有配合物1 - 6在没有激活剂的情况下都能使超螺旋(SC)质粒DNA发生双链断裂。此外,它们对人乳腺癌细胞系(HBL - 100)的细胞毒性比相应的氯配合物1a - 6a更强,并且有潜力作为有效的细胞毒性药物。

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