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反式-二氯二钯(II)和铂(II)配合物与 2-(羟甲基)吡啶和 2-(2-羟乙基)吡啶的合成、结构表征、DNA 结合及体外细胞毒性研究。

trans-Dichloridopalladium(II) and platinum(II) complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine: synthesis, structural characterization, DNA binding and in vitro cytotoxicity studies.

机构信息

Department of Chemistry, Faculty of Arts and Sciences, Uludag University, Gorukle, 16059 Bursa, Turkey.

出版信息

Eur J Med Chem. 2013 Feb;60:386-94. doi: 10.1016/j.ejmech.2012.12.002. Epub 2012 Dec 8.

Abstract

Four trans-palladium(II)- and trans-platinum(II)-chlorido complexes, trans-[PdCl(2)(2-hmpy)(2)] (1), trans-[PtCl(2)(2-hmpy)(2)] (2), trans-[PdCl(2)(2-hepy)(2)] (3) and trans-[PtCl(2)(2-hepy)(2)] (4) (2-hmpy = 2-(hydroxymethyl)pyridine and 2-hepy = 2-(2-hydroxyethyl)pyridine), have been synthesized and characterized by elemental analysis, IR, NMR, and X-ray diffraction. The binding properties of these complexes with fish sperm DNA (FS-DNA) were investigated by UV titration, viscosity, thermal denaturation and electrophoresis measurements. The complexes can bind to FS-DNA and complex 4 exhibits the highest binding constant. Gel electrophoresis assay demonstrates that all the complexes can cleave the pCMV-βgal plasmid DNA to a different degree. The cytotoxic activities of the complexes were tested against four different cancer cell lines. In general, the platinum(II) complexes are more effective than the isostructural palladium(II) complexes. Complex 4 shows high anticancer activity, compared to transplatin, cisplatin, carboplatin and oxaliplatin.

摘要

四种反式钯(II)和反式铂(II)氯代配合物,反式-[PdCl2(2-hmpy)(2)](1)、反式-[PtCl2(2-hmpy)(2)](2)、反式-[PdCl2(2-hepy)(2)](3)和反式-[PtCl2(2-hepy)(2)](4)(2-hmpy=2-(羟甲基)吡啶,2-hepy=2-(2-羟乙基)吡啶),已通过元素分析、IR、NMR 和 X 射线衍射进行了合成和表征。通过紫外滴定、粘度、热变性和电泳测量研究了这些配合物与鱼精 DNA(FS-DNA)的结合特性。这些配合物可以与 FS-DNA 结合,并且配合物 4 具有最高的结合常数。凝胶电泳试验表明,所有配合物都能不同程度地切割 pCMV-βgal 质粒 DNA。测试了这些配合物对四种不同癌细胞系的细胞毒性活性。总的来说,铂(II)配合物比结构相似的钯(II)配合物更有效。与顺铂、卡铂和奥沙利铂相比,配合物 4 表现出很高的抗癌活性。

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