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A new 4-(pyridinyl)-4 H -benzo[ g ]chromene-5,10-dione ruthenium(II) complex inducing senescence in 518A2 melanoma cells
JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2019-06-19 , DOI: 10.1007/s00775-019-01677-y
Madeleine Gold , Yusufi Mujahid , Khursheed Ahmed , Hana Kostrhunova , Jana Kasparkova , Viktor Brabec , Bernhard Biersack , Rainer Schobert

2-Amino-5,10-dihydro-5,10-dioxo-4(pyridine-3-yl)-4H-benzo[g]chromene-3-carbonitrile 5, a cytotoxic lawsone derivative, was reacted with [Ru(p-cymene)Cl2]2 to afford a new Ru(II) ‘piano-stool’ complex 6 which differed from its ligand 5 by a greater selectivity for highly invasive 518A2 melanoma cells over human dermal fibroblasts in MTT cytotoxicity assays, and by inducing senescence rather than apoptosis in the former. DNA is a likely cellular target of complex 6 as it bound, presumably non-covalently, to linear and circular double-stranded DNA in vitro and as ruthenium was found in the lysate of nuclei of treated 518A2 melanoma cells. It also caused a fivefold increase of reactive oxygen species in these cells, originating from a more persistent redox cycling as visualised by cyclic voltammetry.

中文翻译:

新的4-(吡啶基)-4 H-苯并[g]亚甲基-5,10-二酮钌(II)配合物诱导518A2黑色素瘤细胞衰老

使具有细胞毒性的劳森酮衍生物2-氨基-5,10-二氢-5,10-二氧代-4(吡啶-3-基)-4 H-苯并[ g ]亚甲基-3-甲腈5与[Ru(-cymene)Cl 2 ] 2提供一种新的Ru(II)“钢琴凳”复合物6,该化合物与它的配体5的区别在于在MTT细胞毒性试验中对高侵袭性518A2黑色素瘤细胞的选择性比人类真皮成纤维细胞高。前者诱导衰老而不是凋亡。DNA可能是复合物6的细胞靶标因为它在体外可能以非共价方式与线性和环状双链DNA结合,并且在处理过的518A2黑色素瘤细胞核的裂解物中发现了钌。它也导致这些细胞中活性氧的增加五倍,这是由于循环伏安法显示的更持久的氧化还原循环而引起的。
更新日期:2019-06-19
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