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Trans-Pd/Pt(II) saccharinate complexes with a phosphine ligand: Synthesis, cytotoxicity and structure-activity relationship
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2020-03-04 , DOI: 10.1016/j.bmcl.2020.127077
Ceyda Icsel , Veysel T. Yilmaz , Muhittin Aygun , Engin Ulukaya

New trans-[Pd(sac)2(PPhMe2)(DMSO)]·H2O (Pd) and trans-[Pt(sac)2(PPhMe2)2]·H2O (Pt) complexes (sac =saccharinate and PPhMe2 = dimethylphenylphosphine) were synthesized and characterized by elemental analysis, IR, NMR, ESI-MS spectral analyses and X-ray diffraction. The complexes were evaluated for their in vitro cytotoxicity against breast (MCF-7), colon (HCT116) and lung (A549) human cancer cell lines. The ATP viability assay displayed that Pd was biologically inactive, but Pt showed significant anticancer potency on MCF-7 cancer cells, similar to cisplatin. The results suggested that Pt targeted DNA, whereas Pd displayed higher binding affinity towards human serum albumin (HSA). Mechanism of action studies of Pt suggested apoptotic cell death due to significant increase in intracellular ROS (reactive oxygen species) levels, mitochondrial damage and formation of DNA double-strand breaks. Finally, this work represents a new example of potent transplatin anticancer complexes.



中文翻译:

具有膦配体的反式-Pd / Pt(II)糖精复合物:合成,细胞毒性和结构-活性关系

新的反式-[Pd(sac)2(PPhMe 2)(DMSO)]·H 2 O(Pd)和反式-[Pt(sac)2(PPhMe 22 ]·H 2 O(Pt)配合物(sac =合成了糖精和PPhMe 2 =二甲基苯基膦并通过元素分析,IR,NMR,ESI-MS光谱分析和X射线衍射对其进行了表征。评价该复合物对乳腺癌(MCF-7),结肠(HCT116)和肺(A549)人癌细胞系的体外细胞毒性。ATP活力测定显示Pd具有生物惰性,但Pt与顺铂相似,在MCF-7癌细胞上显示出显着的抗癌效力。结果表明Pt靶向DNA,而Pd对人血清白蛋白(HSA)的结合亲和力更高。Pt的作用机理研究表明,由于细胞内ROS(活性氧)水平显着增加,线粒体损伤和DNA双链断裂的形成,凋亡细胞死亡。最后,这项工作代表了有效的跨铂抗癌复合物的新实例。

更新日期:2020-03-05
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