Transferring the concept of multinuclearity to ruthenium complexes for improvement of anticancer activity
- Author(s)
- Christian Hartinger, Marco-Antonio Mendoza Parra, Michael Größl, Alexander Egger, Rene Eichinger, John Mangrum, Nicholas Farrell, Magdalena Maruszak, Patrick J. Bednarski, Franz Klein, Michael Jakupec, Alexey Nazarov, Kay Severin, Bernhard Keppler
- Abstract
Multinuclear platinum anticancer complexes are a proven option to overcome resistance of established anticancer compounds. Transferring this concept to ruthenium complexes led to the synthesis of dinuclear Ru(II)-arene compounds containing a bis(pyridinone)alkane ligand linker. A pronounced influence of the spacer length on the in vitro anticancer activity was found, which is correlated to the lipophilicity of the complexes. IC50 values in the same dimension as for established platinum drugs were found in human tumor cell lines. No cross-resistance to oxoplatin, a cisplatin prodrug, was observed for the most active complex in three resistant cell lines; in fact, a 10-fold reversal of sensitivity in two of the oxoplatin-resistant lines was found. (Bio)analytical characterization of the representative examples showed that the ruthenium complexes hydrolyze rapidly, forming predominantly diaqua species that exhibit affinity toward transferrin and DNA, indicating that both proteins and nucleobases are potential targets.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Chromosome Biology
- External organisation(s)
- Virginia Commonwealth University, Ernst Moritz Arndt Universität Greifswald, École polytechnique fédérale de Lausanne
- Journal
- Journal of Medicinal Chemistry
- Volume
- 52
- Pages
- 916-925
- No. of pages
- 10
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm8013234
- Publication date
- 2009
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301305 Medical chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/1c0efe00-4e56-4c8a-a227-ce9dc4aa35cd