Understanding the interactions of diruthenium anticancer agents with amino acids
- Author(s)
- Alexey A. Nazarov, Maria Grazia Mendoza Parra Ferri, Muhammad Hanif, Bernhard K. Keppler, Paul J. Dyson, Christian G. Hartinger
- Abstract
Abstract: The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-κO)-2-methyl-4-(1H)-pyridinonato-κO4](η
6-p-cymene)-ruthenium(II)}alkane (PyRu
2
n) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein–DNA and DNA–DNA crosslinking ability. We report here studies on the reactions of the diruthenium organometallics PyRu
2
6 and PyRu
2
8 in comparison with a mononuclear analogue PyRu
3 with amino acids using mass spectrometry and NMR spectroscopy. The compounds behave very similarly, independent of the spacer length between the metal center and of the nuclearity of the complexes. Incubation with l-cysteine (Cys) results in fast release of the pyridone ligand, with the Ru complexes able to form Cys adducts. In contrast, l-methionine forms, initially, adducts with the metal centers, but over time, the adducts decompose. Similar behavior was observed for the reaction with l-histidine with [Ru(η
6-p-cymene)(l-histidine)] species detected. Graphical abstract: [Figure not available: see fulltext.].
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Anuchin Research Institute and Museum of Anthropology, University of Auckland, École polytechnique fédérale de Lausanne
- Journal
- Journal of Biological Inorganic Chemistry
- Volume
- 23
- Pages
- 1159-1164
- No. of pages
- 6
- ISSN
- 0949-8257
- DOI
- https://doi.org/10.1007/s00775-018-1597-x
- Publication date
- 10-2018
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/3670f071-7b08-4a76-8db9-660128410ece