Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: comparison of effects of geometry and polyfunctionality on biological activity.
Synthesis, characterization, and cytotoxicity of trifunctional dinuclear platinum complexes: comparison of effects of geometry and polyfunctionality on biological activity.
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DOI：
10.1021/jm990536z
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发表时间：
2000-07
影响因子：
7.3
通讯作者：
Ana Paula Soares Fontes;Ramani Bandarage;Nicholas Farrell;Y. Qu;H. Rauter;Lloyd R. Kelland
中科院分区：
文献类型：
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作者：
Ana Paula Soares Fontes;Ramani Bandarage;Nicholas Farrell;Y. Qu;H. Rauter;Lloyd R. Kelland
报道了两种新型三官能团双核铂配合物[¿PtCl(nh3))(2) -微- nh2 (CH(2))(6) nh2 -¿PtCl（2)(nh3)）¿](+)（1,2/ c，c和1,2/t,c）的合成。描述了它们在对CDDP(顺铂，顺式-[Pt(NH(3))（2)Cl(2)]）敏感和耐药的选定人类肿瘤细胞系中的生物活性，并与它们的双功能类似物[¿顺式/trans-PtCl(NH(3))(2)¿(2)微-NH(2)(CH(2))(6)NH(2)]（2+）的特征进行了比较。三功能双核铂配合物对人类癌细胞具有独特的细胞毒性，在A2780、CH1和41M细胞系中具有低耐药因子。电阻因子取决于铂配位球的几何形状，这表明它们可能与dna结合模式有关。对CDDP抗性细胞系的活性保留以及与CDDP和不同类别的多核铂配合物相比的不同活性谱表明，它们不仅在机制上不同于单核铂配合物，而且每一类多核铂结构可能都有其独特的特征。
The synthesis of two new isomeric trifunctional dinuclear platinum complexes of formula [¿PtCl(NH(3))(2)¿micro-NH(2)(CH(2))(6)NH(2)-¿PtCl(2)(N H(3))¿](+) (1, 2/c,c and 1,2/t,c) is reported. Their biological activity in selected human tumor cell lines sensitive and resistant to CDDP (cisplatin, cis-[Pt(NH(3))(2)Cl(2)]) is described and compared with the profile for their bifunctional analogues, [¿cis/trans-PtCl(NH(3))(2)¿(2)micro-NH(2)(CH(2))(6)NH(2)](2+ ). The trifunctional dinuclear platinum complexes showed a unique profile of cytotoxicity against human cancer cell lines, with low resistance factors in A2780, CH1, and 41M cell lines. The resistance factor is dependent on the geometry of the Pt coordination spheres - suggesting that these may be associated with DNA-binding modes. Retention of activity against CDDP-resistant cell lines and a different spectrum of activity compared to CDDP and also within different classes of polynuclear platinum complexes suggest that not only are they mechanistically different from mononuclear platinum complexes but also each individual class of polynuclear platinum structure may have its own unique character.