University of Kragujevac, Centre for Molecular Medicine, Faculty of Medicine, S. Markovića 69, 34000 Kragujevac, Serbia.
J Inorg Biochem. 2010 Sep;104(9):944-9. doi: 10.1016/j.jinorgbio.2010.04.014. Epub 2010 May 8.
We have studied the kinetics of the complex formation of gold(III) complexes, AuCl(2)(en) (dichlorido(ethylenediamine)aurate(III)-ion) and [AuCl(2)(SMC)] (dichlorido (S-methyl-l-cysteine)aurate(III)) with four biologically N-donor nucleophiles. It was shown that studied ligands have a high affinity for gold(III) complex, which may have important biological implications, since the interactions of Au(III) with DNA is thought to be responsible for the anti-tumour activity. The [AuCl(2)(SMC)] complex is more reactive than AuCl(2)(en). L-His reacts faster than the other N-donor nucleophiles in the reaction with AuCl(2)(en), but in the reaction with [AuCl(2)(SMC)] 5'-GMP is the best nucleophile. Gold(III) complexes are much more reactive than Pt(II) complexes with the same nucleophiles. The activation parameters for all studied reactions suggest an associative substitution mechanism. The cytotoxicity of gold(III) complexes, AuCl(2)(en), [AuCl(2)(SMC)] and AuCl(2)(DMSO)(2) was evaluated in vitro against chronic lymphocytic leukemia cells, obtained from blood of patients with chronic lymphocytic leukemia (CLL). The AuCl(2)(en) complex show comparable cytotoxicity profiles compared to cisplatin.
我们研究了金(III)配合物与四种生物 N-供体亲核试剂的配合物形成动力学,[AuCl(2)(en)]+(二氯(乙二胺)金(III)离子)和[AuCl(2)(SMC)] (二氯(S-甲基-L-半胱氨酸)金(III))。结果表明,研究配体对金(III)配合物具有高亲和力,这可能具有重要的生物学意义,因为 Au(III)与 DNA 的相互作用被认为是抗肿瘤活性的原因。[AuCl(2)(SMC)]配合物比[AuCl(2)(en)]+更具反应性。L-His 在与[AuCl(2)(en)]+的反应中比其他 N-供体亲核试剂反应更快,但在与[AuCl(2)(SMC)]的反应中 5'-GMP 是最好的亲核试剂。金(III)配合物比具有相同亲核试剂的 Pt(II)配合物具有更高的反应性。所有研究反应的活化参数表明,反应遵循缔合取代机制。金(III)配合物[AuCl(2)(en)]+、[AuCl(2)(SMC)]和[AuCl(2)(DMSO)(2)]+的体外细胞毒性在慢性淋巴细胞白血病细胞(CLL)中进行了评估,这些细胞来自慢性淋巴细胞白血病患者的血液。[AuCl(2)(en)]+配合物与顺铂具有可比的细胞毒性谱。