Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255, USA.
Chem Res Toxicol. 2009 Oct;22(10):1705-12. doi: 10.1021/tx900180v.
A new class of platinum(II) coordination complexes and their dye tagged conjugates has been synthesized from N-substituted diaminocyclohexane ligands. The in vitro anticancer activities of the platinum compounds have been validated against the breast cancer cell-line MCF-7 and the normal cell-line MCF-10A via sulforhodamine B and colony formation assay. The platinum compounds and the corresponding metal-free ligands exhibited higher drug efficiencies than cisplatin and oxaliplatin against MCF-7 cells. Cellular uptake and DNA-bound Pt were demonstrated by atomic absorption spectroscopy. The platinum complexes displayed increased cellular accumulation and DNA binding as compared with cisplatin. Real-time reverse transcription polymerase chain reaction assay was employed to investigate drug effects on mRNA expression in MCF-7 cells. The results indicated that the study compounds are effective in regulating cyclin D1, Bcl-2, and p53 genes; yet, oxaliplatin is less effective in manipulating those genes. The luminescent probe that was integrated into the platinum complexes made it possible to monitor cellular drug distribution using optical imaging. Targeting of tumor cell nuclei by the study compounds was confirmed by confocal microscopy. Taken together, these new platinum(II)-based antitumor agents are different from marketed platinum drugs in several critical aspects and could have potential in cancer therapy.
一类新型的铂（II）配位化合物及其染料标记缀合物已由取代的二氨基环己烷配体制备。通过磺基罗丹明 B 和集落形成试验，对铂化合物的体外抗癌活性进行了验证，以乳腺癌细胞系 MCF-7 和正常细胞系 MCF-10A 为对象。铂化合物及其相应的金属自由配体对 MCF-7 细胞的药物效率均高于顺铂和奥沙利铂。通过原子吸收光谱法证明了铂配合物的细胞摄取和 DNA 结合的 Pt。与顺铂相比，铂配合物的细胞积累和 DNA 结合增加。实时逆转录聚合酶链反应试验被用来研究药物对 MCF-7 细胞中 mRNA 表达的影响。结果表明，这些研究化合物能有效调节细胞周期蛋白 D1、Bcl-2 和 p53 基因；而奥沙利铂在操纵这些基因方面的效果则较差。将发光探针整合到铂配合物中，使得使用光学成像来监测细胞内药物分布成为可能。通过共聚焦显微镜证实了研究化合物对肿瘤细胞核的靶向性。总之，这些新型的基于铂的抗肿瘤药物在几个关键方面与市场上的铂类药物不同，可能在癌症治疗方面具有潜力。
