Functionalization of ruthenium(II)(ų6-p-cymene)(3-hydroxy-2-pyridone) complexes with (thio)morpholine: Synthesis and bioanalytical studies

Muhammad Hanif, Samuel M. Meier, Zenita Adhireksan, Helena Henke, Sanela Martic, Sanam Movassaghi, Mahmoud Labib, Wolfgang Kandioller, Stephen M.F. Jamieson, Michaela Hejl, Michael A. Jakupec, Heinz Bernhard Kraatz, Curt A. Davey, Bernhard K. Keppler, Christian G. Hartinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Hydroxypyr(id)ones constitute an emerging platform for the design of drug molecules, owing to their favorable biocompatibility and toxicity profiles. Herein, [RuII6-p-cymene)] complexes with 3-hydroxy-2-pyridinone functionalized with morpholine and thiomorpholine, as a means often used in medicinal chemistry to alter the physicochemical properties of drug compounds, are reported. The compounds underwent hydrolysis of the Ru@Cl bond and the aqua species were stable for up to 48 h in aqueous solution, as observed by 1H NMR spectroscopy and ESI-MS. The compounds formed adducts with amino acids and proteins through cleavage of the pyridinone ligand. Binding experiments to the nucleosome core particle by means of X-ray crystallography revealed similar reactivity and exclusive binding to histidine moieties of the histone proteins. Preliminary cyclin-dependent kinase 2 (CDK2)/cyclinA kinase inhibitory studies revealed promising activity similar to that of structurally related organometallic compounds.

Original languageEnglish (US)
Pages (from-to)841-847
Number of pages7
Issue number6
StatePublished - Jun 1 2017
Externally publishedYes


  • Antitumor agents
  • Bioorganometallic chemistry
  • Medicinal chemistry
  • Ruthenium
  • Synthesis design

ASJC Scopus subject areas

  • Chemistry(all)


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