X-ray Absorption Near Edge Structure Spectroscopy to Resolve the in Vivo Chemistry of the Redox-Active Indazolium trans-[Tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019)
- Author(s)
- Alfred Hummer, Petra Heffeter, Walter Berger, Martin Filipits, David Batchelor, Gabriel Büchel, Michael Jakupec, Bernhard Keppler, Annette Rompel
- Abstract
Indazolium trans-[tetrachlorobis(1H-indazole)-ruthenate(III)] (1, KP1019) and its analogue sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (2, KP1339) are promising redox-active anticancer drug candidates that were investigated with X-ray absorption near edge structure spectroscopy. The analysis was based on the concept of the coordination charge and ruthenium model compounds representing possible coordinations and oxidation states in vivo. 1 was investigated in citrate saline buffer (pH 3.5) and in carbonate buffer (pH 7.4) at 37 degrees C for different time intervals. Interaction studies on 1 with glutathione in saline buffer and apo-transferrin in carbonate buffer were undertaken, and the coordination of 1 and 2 in tumor tissues was studied too. The most likely coordinations and oxidation states of the compound under the above mentioned conditions were assigned. Microprobe X-ray fluorescence of tumor thin sections showed the strong penetration of ruthenium into the tumor tissue, with the highest concentrations near blood vessels and in the edge regions of the tissue samples.
- Organisation(s)
- Department of Biophysical Chemistry, Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien, Karlsruher Institut für Technologie
- Journal
- Journal of Medicinal Chemistry
- Volume
- 56
- Pages
- 1182-1196
- No. of pages
- 15
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/jm301648f
- Publication date
- 2013
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301206 Pharmacology, 301305 Medical chemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/9fcbdad9-925e-438d-989b-9ee9dd14024f