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

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Abstract

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.

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Acknowledgements

R. S. thanks the Deutsche Forschungsgemeinschaft (DFG) for a grant (Scho 402/12-2), H. K., J. K. and V. B. were supported by the Czech Science Foundation (Grant 17–05302S).

Funding

Deutsche Forschungsgemeinschaft Grant Scho 402/12; Czech Science Foundation Grant 17–05302S.

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Authors and Affiliations

  1. Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440, Bayreuth, Germany

    Madeleine Gold, Bernhard Biersack & Rainer Schobert

  2. Department of Chemistry, Abeda Inamdar Senior College, 2390-B, K.B. Hidayatullah Road, Pune, 411001, India

    Yusufi Mujahid & Khursheed Ahmed

  3. Institute of Biophysics, Czech Academy of Sciences, Kralovopolska 135, 61265, Brno, Czech Republic

    Hana Kostrhunova, Jana Kasparkova & Viktor Brabec

  4. Department of Biophysics, Faculty of Science, Palacky University, Slechtitelu 27, 78371, Olomouc, Czech Republic

    Jana Kasparkova

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Stability tests via 1H-NMR for compound 6; electrophoretic mobility shift assays; interaction with pBR322 plasmid DNA; uptake of complex 6 by 518A2 melanoma cells; cyclic voltammetry; caspase-3/7 activity assays; This material is available free of charge via the Internet at https://link.springer.com 1 (PDF 1103 kb)

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Gold, M., Mujahid, Y., Ahmed, K. et al. A new 4-(pyridinyl)-4H-benzo[g]chromene-5,10-dione ruthenium(II) complex inducing senescence in 518A2 melanoma cells. J Biol Inorg Chem 24, 647–657 (2019). https://doi.org/10.1007/s00775-019-01677-y

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