Functionalization of ruthenium(II)(ų <sup>6</sup>-p-cymene)(3-hydroxy-2-pyridone) complexes with (thio)morpholine
- Author(s)
- 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
- Abstract
Hydroxypyr(id)ones constitute an emerging platform for the design of drug molecules, owing to their favorable biocompatibility and toxicity profiles. Herein, [Ru
II(ų
6-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.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Analytical Chemistry
- External organisation(s)
- University of Auckland, Nanyang Technological University (NTU), Oakland University, University of Toronto
- Journal
- Chempluschem
- Volume
- 82
- Pages
- 841-847
- No. of pages
- 7
- ISSN
- 2192-6506
- DOI
- https://doi.org/10.1002/cplu.201700050
- Publication date
- 06-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104002 Analytical chemistry
- Keywords
- ASJC Scopus subject areas
- General Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/aa62b5a2-12c3-4eb7-8152-0653ccf32913