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二硫代氨基甲酸盐衍生物的二亚胺铂(II)和钯(II)配合物作为潜在的抗肿瘤剂:合成、表征、细胞毒性及详细的DNA结合研究

Diimine platinum(II) and palladium(II) complexes of dithiocarbamate derivative as potential antitumor agents: synthesis, characterization, cytotoxicity, and detail dna-binding studies.

作者信息

Mansouri-Torshizi H, Moghaddam M I, Divsalar A, Saboury A A

机构信息

Department of Chemistry, University of Sistan & Baluchestan, Zahedan, Iran.

出版信息

J Biomol Struct Dyn. 2009 Apr;26(5):575-86. doi: 10.1080/07391102.2009.10507273.

Abstract

The synthesis and chemical characterization of two structurally related platinum(II) and palladium(II) complexes, [M(2,2'-bipyridine)(morpholinedithiocarbamate)]NO(3) or [M(bpy)(mor-dtc)]NO(3), where M = Pt(II) or Pd(II), are described. Studies of anti-tumor activities of these complexes against human cell tumor lines (K(562)) have been carried out. They show 50% cytotoxic concentration (Cc(50)) values much lower than that of cisplatin. Both of these water soluble complexes have been shown to interact with calf thymus DNA (ct-DNA) using difference absorption-, fluorescence-, and circular dichroism-titration techniques. These studies showed that both complexes exhibit cooperative binding and presumably intercalate in DNA. These complexes unexpectedly denature DNA at very low concentrations (50-100 microM). Several binding and thermodynamic parameters are also described.

摘要

描述了两种结构相关的铂(II)和钯(II)配合物[M(2,2'-联吡啶)(吗啉二硫代氨基甲酸盐)]NO₃或[M(bpy)(mor-dtc)]NO₃(其中M = Pt(II)或Pd(II))的合成及化学表征。已对这些配合物针对人细胞肿瘤系(K(562))的抗肿瘤活性进行了研究。它们显示出50%细胞毒性浓度(Cc(50))值远低于顺铂。使用差分吸收、荧光和圆二色性滴定技术已表明这两种水溶性配合物都能与小牛胸腺DNA(ct-DNA)相互作用。这些研究表明这两种配合物都表现出协同结合且可能插入到DNA中。这些配合物在非常低的浓度(50 - 100微摩尔)下意外地使DNA变性。还描述了几个结合和热力学参数。

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