Cytotoxic effect, generation of reactive oxygen/nitrogen species and electrochemical properties of Cu(ii) complexes in comparison to half-sandwich complexes of Ru(ii) with aminochromone derivatives

Abstract

This paper describes the synthesis of new 6-aminoflavone (6AFl (3)) and 6-aminochromone (6AC (4)) complexes with Cu(II) and Ru(II) ions ([Cu(6AC)₂Cl₂] (3a), [Cu(6AFl)₂Cl₂] (4a), [Ru(p-cymene)(6AC)Cl₂] (4b)) and comparison of their properties with the previously described 7-aminoflavone (7AFl (1)) and 7-amino-2-methylchromone (7A2MC (2)) analogues. The cytotoxic effect of all these complexes against two human leukaemia cell lines (HL-60 and NALM-6), melanoma WM-115 cells and COLO205 cells, is determined. The cytotoxicity of copper(II) complexes, especially [Cu(6AFl)₂Cl₂] (3a) was higher than ruthenium(II) complexes with the same ligands. Their cytotoxic potency was also stronger in comparison to the referential agents like cisplatin. The pro-oxidative properties were determined for the most active complexes and their ability to generate ROS (reactive oxygen species)/RNS (reactive nitrogen species) in cancer cells was confirmed. The type of ligand and the chemical structure of the tested complexes had an influence on the level of ROS/RNS generated in cancer cells. The redox properties of the copper complex compounds were evaluated by cyclic voltammetry, and compared with the data for Ru(II) complexes. The reduction and oxidation processes of Ru(III)/Ru(II) and Cu(II)/Cu(I) were described as quasi-reversible.