Structure-Activity Relationships of Targeted Ru-II(eta(6)-p-Cymene) Anticancer Complexes with Flavonol-Derived Ligands
- Author(s)
- Andrea Kurzwernhart, Wolfgang Kandioller, Simone Bächler, Caroline Bartel, Sanela Martic, Magdalena Buczkowska, Gerhard Mühlgassner, Michael Jakupec, Heinz-Bernhard Kraatz, Patrick J. Bednarski, Vladimir Arion, Doris Marko, Bernhard Keppler, Christian G. Hartinger
- Abstract
Ru-II(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized Ru-II(eta(6)-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multitargeted anticancer agents. To validate this concept, studies on the mode of action of the complexes were conducted which indicated that they form covalent bonds to DNA, have only minor impact on the cell cycle, but inhibit CDK2 and topoisomerase Ha in vitro. The cytotoxic activity was determined in human cancer cell lines, resulting in very low IC50 values as compared to other Ru-II(arene) complexes and showing a structure-activity relationship dependent on the substitution pattern of the flavonol ligand. Furthermore, the inhibition of cell growth correlates well with the topoisomerase inhibitory activity. Compared to the flavonol ligands, the Ru-II(eta(6)-p-cymene) complexes are more potent antiproliferative agents, which can be explained by potential multitargeted properties.
- Organisation(s)
- Department of Inorganic Chemistry, Department of Food Chemistry and Toxicology
- External organisation(s)
- University of Western Ontario, Ernst Moritz Arndt Universität Greifswald, University of Auckland
- Journal
- Journal of Medicinal Chemistry
- Volume
- 55
- Pages
- 10512-10522
- No. of pages
- 11
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm301376a
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301305 Medical chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/fe2bab29-8b47-4d3f-9f4f-0b67cd1af751