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A new 4-(pyridinyl)-4H-benzo[g]chromene-5,10-dione ruthenium(II) complex inducing senescence in 518A2 melanoma cells.

Autoři: Gold M., Mujahid J., Ahmed K., Kostrhunova H., Kasparkova J., Brabec V., Biersack B., Schober R.Publikováno : Journal of Biological Inorganic Chemistry 24(5), 647-657Rok: 2019

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 visualized by cyclic voltammetry.


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