New redox-active Cu complexes with tridentate chelating ligands based on 2-thioimidazol-4-ones as potential antiproliferative agents

Abstract

A synthetic approach to the first hybride triazolyl-pyridyl-imidazolone ligands with redox-active auxiliary groups was developed. These tridentate ligands may be used to obtain copper coordination compounds of two structural types, differing in the oxidation state of the copper ion and the geometry of its environment. These complexes were successifully synthesised and characterized by NMR, CV, RDE, HRMS, EPR, and XRD data. All coordination compounds exhibited cytotoxic activity against the MCF-7 and A549 tumor cell lines, exceeding significantly the IC50 of the free ligands. The two most promising complexes, 11c and 15c, demonstrated cytotoxicity at low micromolar concentrations, in vitro selectivity better than cisplatin, and inhibition of tumor growth in vivo. The mechanism of cytotoxic action of these complexes is most likely associated with oxidative cleavage of DNA under redox reactions involving metal ions in coordination compounds.