Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione.
Synthesis, characterization and biological activity of Pt(II) and Pt(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione.
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DOI：
10.1016/j.ejmech.2007.06.025
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发表时间：
2008-05
影响因子：
6.7
通讯作者：
A. Bakalova;H. Varbanov;R. Buyukliev;G. Momekov;D. Ferdinandov;S. Konstantinov;D. Ivanov
中科院分区：
文献类型：
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作者：
A. Bakalova;H. Varbanov;R. Buyukliev;G. Momekov;D. Ferdinandov;S. Konstantinov;D. Ivanov
合成了5-甲基-5-（4-吡啶基）-2，4-咪唑啉二酮与不同卤离子的铂（II）和铂（IV）配合物，通式为[PtL 2X2]和[PtL 2Cl 4]，其中L为有机配体，X为Cl-，Br-，J-。通过元素分析、红外光谱、核磁共振氢谱、碳谱和摩尔电导率分析确定了配合物的分子式。这些配合物的细胞毒作用进行了研究，对一些人肿瘤细胞系。新合成的cis-[PtL_2Cl_2]对SKW-3、MCF-7、EJ、U-266等肿瘤细胞株有一定的细胞毒活性，而cis-[PtL_2Br_2]、trans-[PtL_2I_2]活性较低。较高的氧化态复合物顺式-[PtL 2Cl 4]在所有细胞系中无活性，但在SKW-3中，在抗坏血酸共同给药后观察到细胞毒性的一些增强，但在与还原型谷胱甘肽或N-乙酰半胱氨酸联合治疗时观察不到。DNA片段化分析显示，二氯类似物的细胞毒性，其特征在于与其他复合物相比具有上级活性，是通过诱导凋亡细胞死亡介导的。
New platinum(II) and platinum(IV) complexes with 5-methyl-5(4-pyridyl)-2,4-imidazolidenedione and various halogen ions with general formula [PtL2X2] and [PtL2Cl4], where L is the organic ligand and X is Cl−, Br−, J−, were synthesized. The molecular formulae of all the complexes were confirmed by elemental analysis, IR,1H,13C NMR spectral analyses and molar conductivity. The cytotoxic effects of these complexes were examined on some human tumor cell lines. The newly synthesized cis-[PtL2Cl2] exerted cytotoxic activity against SKW-3, MCF-7, EJ, U-266 tumor cell lines, while cis-[PtL2Br2], trans-[PtL2I2] were less active. The higher oxidation state complex cis-[PtL2Cl4] was inactive in all cell lines but in SKW-3 some augmentation of the cytotoxicity was seen after co-administration of ascorbic acid but not when treated in combination with reduced glutathione or N-acetylcysteine. A DNA-fragmentation analysis revealed that the cytotoxicity of the dichloro analogue, characterized with superior activity compared to the other complexes, is mediated by induction of apoptotic cell death.