Abstract (eng)
Since the discovery of cisplatin, platinum(II) compounds have become an integral part of anticancer chemotherapy. Despite their remarkable cure rates for some types of cancer, it is necessary to search for alternatives due to the severe side effects of approved platinum compounds and the resistance of some tumor types.
As known for several years ruthenium(II) and ruthenium(III) compounds are promising anti-cancer agents, although the mode of action is still controversial.
At least since the anti-angiogenic and anti-invasive properties of NAMI-A were in part reported to NO capturing, NO, which plays an important role in organism as signaling molecule, in blood pressure regulation, inflammatory response and in necrosis and apoptosis, is an interesting ligand for potential anticancer agents. Moreover ruthenium shows a well described affinity to NO.
Amino acids are the most important biological ligands with low molecular weight in the body as well as in cell culture experiments, nevertheless very little is known about the reactivity of amino acids towards ruthenium-nitrosylcomplexes. We intend to close that gap and therefore a series of ruthenium-nitrosylcomplexes with amino acids, Bu4N[RuCl3NO(L)] (L = L-Ala, L-Val, Gly, L-Ser, L-Thr, L-Tyr, L-Pro, D-Pro), was prepared and characterized by 1H NMR, ESI MS, UV-vis, ATR IR spectroscopy, cyclic voltammetry, elemental analysis and X-ray crystallography. Furthermore cell culture experiments with three human cancer cell lines were performed. The IC50 values were determined.
Na2[RuCl5NO].6H2O, 1.5 eq amino acid and 2 eq Bu4NCl were dissolved in n-butanol and refluxed for 1.5 hours. To obtain the L-Tyr and Gly complexes the n-butanol solutions were transferred into a baker. The solutions were filtrated after 24 hours and after several days the desired product crystallized. To obtain the other complexes n-butanol was evaporated, the remaining oil was dried in vacuo and dissolved in water. Crystals formed after several days.