DNA interactions of dinuclear RuII arene antitumor complexes in cell-free media
- Author(s)
- Olga Novakova, Alexey Nazarov, Christian Hartinger, Bernhard Keppler, Viktor Brabec
- Abstract
We recently synthesized and characterized water-soluble dinuclear RuII arene complexes, in which two {(?6-p-isopropyltoluene)RuCl[3-(oxo-?O)-2-methyl-4-pyridinonato-?O4]} units were linked by flexible chains of different length [(CH2)n (n = 4, 6, 8, 12)]. These new dinuclear ruthenium drugs were found to exert promising cytotoxic effects in human cancer cells. In the present work DNA modifications by these new dinuclear RuII arene compounds, which differed in the length of the linker between the two RuII centers, were examined by biochemical and biophysical methods. The complexes bind DNA forming intrastrand and interstrand cross-links in one DNA molecule in the absence of proteins. An intriguing aspect of the DNA-binding mode of these dinuclear RuII compounds is that they can cross-link two DNA duplexes and also proteins to DNA-a feature not observed for other antitumor ruthenium complexes. Thus, the concept for the design of interhelical and DNA-protein cross-linking agents based on dinuclear RuII arene complexes with sufficiently long linkers between two Ru centers may result in new compounds which exhibit a variety of biological effects and can be also useful in nucleic acids research.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Czech Academy of Sciences
- Journal
- Biochemical Pharmacology
- Volume
- 77
- Pages
- 364-374
- No. of pages
- 11
- ISSN
- 0006-2952
- DOI
- https://doi.org/10.1016/j.bcp.2008.10.021
- Publication date
- 2009
- 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/0783d56a-aa48-4ccb-ae71-67bc3d5e52dd