Iron-salophen complexes involving azole-derived ligands: A new group of compounds with high-level and broad-spectrum in vitro antitumor activity.

A series of iron(II/III) salophen (salph) complexes involving monodentate azole-derived ligands, having the composition [Fe(II)(salph)(HL1)] (1) and [Fe(III)(salph)(L)] (2-6), where HL1=imidazole, L=1,2,4-triazol-1-ido (L2), benzo[d][1,2,3]triazol-1-ido (L3), 5-aminotetrazol-1-ido (L4), 5-phenyltetrazol-1-ido (L5), and 5-methyltetrazol-1-ido (L6) ligand, was prepared and characterized by elemental analyses, infrared, Mössbauer and X-ray photolelectron spectroscopy, magnetic data and electrospray-ionization mass spectrometry. X-ray structure of 1 revealed a distorted square-pyramidal geometry in the vicinity of the iron(II) atom. The complexes were evaluated for their in vitro antitumor activity against the panel of six human cancer cell lines (HOS, MCF7, A549, HeLa, A2780 and G-361) and were found to be highly cytotoxic, showing the best IC50 value of 58nM for [Fe(III)(salph)(L6)] (6) against the ovarian carcinoma A2780 cell line, being 200-times more effective than cisplatin. In vitro cytotoxicity of complexes 1-6 on primary culture of human hepatocytes and calf-thymus DNA (CT-DNA) binding studies using the fluorescence titration were also performed.