Influence of the π-coordinated arene on the anticancer activity of ruthenium(II) carbohydrate organometallic complexes

  • Front Chem. 2013 Oct 31:1:27. doi: 10.3389/fchem.2013.00027.
Muhammad Hanif  1 ,  Samuel M Meier  2 ,  Alexey A Nazarov  3 ,  Julie Risse  4 ,  Anton Legin  5 ,  Angela Casini  6 ,  Michael A Jakupec  2 ,  Bernhard K Keppler  2 ,  Christian G Hartinger  7
Affiliations
  • 1. School of Chemical Science, The University of Auckland Auckland, New Zealand ; Institute of Inorganic Chemistry, University of Vienna Vienna, Austria ; Department of Chemistry, COMSATS Institute of Information Technology Abbottabad, Pakistan.
  • 2. Institute of Inorganic Chemistry, University of Vienna Vienna, Austria ; Research Platform "Translational Cancer Therapy Research", University of Vienna Vienna, Austria.
  • 3. Institute of Inorganic Chemistry, University of Vienna Vienna, Austria ; Department of Chemistry, Moscow State University Moscow, Russia ; Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
  • 4. Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne Lausanne, Switzerland.
  • 5. Institute of Inorganic Chemistry, University of Vienna Vienna, Austria.
  • 6. Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen Groningen, Netherlands.
  • 7. School of Chemical Science, The University of Auckland Auckland, New Zealand ; Institute of Inorganic Chemistry, University of Vienna Vienna, Austria ; Research Platform "Translational Cancer Therapy Research", University of Vienna Vienna, Austria.
PMID: 24790955 DOI: 10.3389/fchem.2013.00027
Abstract

The synthesis and in vitro cytotoxicity of a series of Ru(II)(arene) complexes with carbohydrate-derived phosphite ligands and various arene co-ligands is described. The arene ligand has a strong influence on the in vitro Anticancer activity of this series of compounds, which correlates fairly well with cellular accumulation. The most lipophilic compound bearing a biphenyl moiety and a cyclohexylidene-protected carbohydrate is the most cytotoxic with unprecedented IC50 values for the compound class in three human Cancer cell lines. This compound shows reactivity to the DNA model nucleobase 9-ethylguanine, but does not alter the secondary structure of plasmid DNA, indicating that Other biological targets are responsible for its cytotoxic effect.

Keywords
anticancer activity; bioorganometallic chemistry; carbohydrates; phosphorus ligands; ruthenium arene compounds.
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