@conference{
author = "Radomirović, Mirjana Ž. and Stanić-Vučinić, Dragana and Nikolić, Stefan and Mihailović, Jelena and Ćirković-Veličković, Tanja and Grgurić Šipka, Sanja",
year = "2019",
abstract = "Objective. In contrast to platinum-based antitumour compounds, the mode of action of ruthenium-based compounds is via protein targets involved in cellular signaling pathways and the histone proteins. As proteins are the first potential binding targets for the complexes in the bloodstream after their intravenous administration, interactions of anticancer therapeutics with proteins are very important to be investigated with aim to elucidate their pharmacokinetic pathways. Four half-sandwich ruthenium(II)-cymene complexes, developed earlier and with promising cytotoxic activity, are investigated for their interactions with proteins, cytochrome c and lysozyme.
Material and Methods. Ruthenium(II)-cymene complexes were incubated for 24 and 48 h at 37 °C in the presence of cytochrome c and lysozyme, both in 20 mM ammonium hydrogen carbonate pH 7.4 and water. High-resolution LTQ-Orbitrap ESI MS was used to monitor the adducts formed between ruthenium complexes and proteins.
Results. The complexes with two Cl- ligands have shown higher reactivity to proteins than those with only one, and were more reactive toward cytochrome c in comparison to lysozyme. The complex with S,N-chelating ligand was less reactive to proteins than one with O,N-chelating ligand. Species initially coordinating the proteins are most likely dehalogenated complexes. During the time, vivid ligand exchange of non-arene organic ligand L with CO32- and OH- takes place after initial formation of protein adducts. In water, only dehalogenated adducts were identified suggesting that in vivo, in the presence of various anions, dynamic ligand exchange could be expected generating different intermediate protein species.
Conclusions. Protein reactivity toward Ru(II) complexes is determined by protein structure and ligands in Ru(II) coordination sphere, but this reactivity should be described from both kinetics, as well as stability aspect. In extracellular or intracellular milieu, ability of metal binding ligands (such as carbonate ions) to bind and to leave, determinate both the extent and mechanism of the binding of ruthenium complexes to the target biomacromolecules for cancer therapy.",
publisher = "Faculty of Sciences, University of Novi Sad, Serbian Proteomics Assosication",
journal = "V SePA symposium: Proteomics in the analysis of food, environmental protection and medical research, Novi Sad, Serbia, 31st May, 2019. In: The Book of Abstracts",
title = "Lysozyme and Cytochrome C adducts of ruthenium(II)-cymene complexes",
pages = "P2-P2",
url = "https://hdl.handle.net/21.15107/rcub_cherry_6038"
}
