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

•Iron-salophen complexes involving azole-derived ligands are reported.•Complexes showed substantial in vitro cytotoxicity against six human cancer cell lines.•Complexes showed lowered in vitro cytotoxicity against healthy human hepatocytes.•Complexes showed moderate CT-DNA binding.

A series of iron(II/III) salophen (salph) complexes involving monodentate azole-derived ligands, having the composition [FeII(salph)(HL1)] (1) and [FeIII(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 58 nM for [FeIII(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.

Graphical abstractIron(II/III) salophen complexes, involving monodentate azole-derived ligands, were prepared, characterized, and screened for in vitro antitumor activity on six human cancer cell lines and healthy human hepatocytes. All the compounds were found to be highly cytotoxic, showing the best IC50 value of 58 nM, being 200-times more effective than cisplatin.Figure optionsDownload full-size imageDownload as PowerPoint slide