Abstract (eng)
Nowadays ruthenium complexes seem to be the most promising alternatives to platinum complexes in the research field of metal-based anticancer compounds. The possibility to tune different properties of ruthenium, such as redox potential, substitution rate or ligand affinity, and increasing knowledge about the biological activity of ruthenium complexes makes this metal worth of investigation. The discovery that nitric oxide is one of the most important physiological regulators had a stimulating effect on the coordination and biological chemistry of this non-innocent ligand. NO plays an important role in many different biological processes, such as neurotransmission, blood pressure control, antioxidant action and immunological responses. The control of NO concentration, which is needed to obtain the required effect, could be achieved with carriers like metal complexes. The controlled NO-releasing or scavenging complexes are, therefore, of great interest for medical purposes. It has been reported that in several types of cancer the apoptosis of the cancer cells is greatly increased in the presence of nitric oxide. Having the metal complex with nitrosyl could induce the anticancer activity or improve the already observed effects.
Ruthenium compounds with one and two azole heterocycles (NAMI-A and KP1019 analogues), which have been synthesized many years ago, are currently studied in phases I-II clinical trials as potential anticancer drugs. Combining those promising compounds with the non-innocent ligand NO gives the opportunity to create metal-nitrosyls with encouraging properties. Of particular interest is the synthesis of ruthenium-nitrosyl complexes with four azole heterocycles. The higher azole-to-chloride ratio decreases the reduction potential of those compounds, which results in higher antiproliferative activity.
The aim of this work was the synthesis and characterisation of ruthenium nitro and nitrosyl compounds with four azole heterocycles, their electrochemical studies and investigation of the stability of Ru-NO bond.