Biomolecule binding vs. anticancer activity: Reactions of Ru(arene)[(thio)pyr-(id)one] compounds with amino acids and proteins
- Author(s)
- Samuel Matthias Meier, Wolfgang Kandioller, Bernhard Keppler, Christian Hartinger
- Abstract
The interactions of the ruthenium(arene) complexes [chlorido(eta(6)-p-cymene)(2-methyl-3-(oxo-kappa O)-4H-pyran-4-onato-kappa O)ruthenium(II)] 1, [chlorido(eta(6)-p-cymene)(2-methyl-3-(oxo-kappa O)-4H-thiopyran-4-onato-kappa S)ruthenium(II)] 2 and [chlorido(eta(6)-p-cymene){N-[(ethoxycarbonyl)methyl]-3-(oxo-kappa O)-1H-pyrid-2-onato-kappa O}ruthenium(II)] 3 with biomolecules such as L-methionine (Met) and ubiquitin (Ub) were investigated by electrospray ionization (ESI) ion trap mass spectrometry (MS). These Ru-II compounds were shown to exhibit anticancer activity which varies depending on the (thio)pyr(id)onato ligands. Compounds 1 and 3 reacted readily with the model protein Ub to yield stable [Ub + Ru(p-cym)] adducts (p-cym = eta(6)-p-cymene), whereas 2 was converted only to a minor degree. The protein adduct formation is reversible by incubation with N- and S-donor systems, the latter being more efficient. From these studies, an inverse correlation between metallodrug-protein interaction and cytotoxicity against human tumor cell lines was derived, where low protein binding ability is indicative of increased cytotoxic activity.
- Organisation(s)
- Department of Inorganic Chemistry
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 108
- Pages
- 91-95
- No. of pages
- 5
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/j.jinorgbio.2011.08.011
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 106002 Biochemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/ffa34ed7-ca1b-4aa9-9b8d-c0344db744bf