Synthesis, X-ray structure and strong in vitro cytotoxicity of novel organoruthenium complexes

•New organoruthenium complexes and ligands have been reported.•Single crystal X-ray structure diffraction analysis confirms a piano-stool geometry of complex.•These complexes show strong in vitro cytotoxicity.•Cell cycle arrest and apoptosis are responsible for cytotoxicity of these complexes.

Two p-cymene ruthenium chlorido complexes containing isobutyl (C1) and isoamyl (C2) esters of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid as ligands were prepared from p-cymene ruthenium dichloride dimer and corresponding ester. All compounds have been characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR spectroscopy. Single crystal X-ray structure diffraction analysis of C1 shows the usual piano-stool geometry of complexes, with coordination of ester ligand via nitrogen donor atoms. Ligands exhibit moderate anticancer activity (IC50 > 50 μM), while the complexes were significantly more cytotoxic towards various cancer cell lines, including B16, A375, HCT116, A549 and MCF7 cells (IC50 min.–max. 2.9–8.0 μM). We stress that cisplatin resistant HCT116 cell line was highly sensitive to the treatment with C1 and C2 (IC50 values: 4.4 and 5.5 μM versus IC50 > 120 μM for cisplatin). In parallel, primary fibroblasts-MRC-5 were remarkably less affected by these compounds.

Graphical abstractOrganoruthenium complexes containing new esters of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid have been synthesized and structurally characterized by IR, 1H NMR, 13C NMR, mass spectrometry and single-crystal X-ray diffraction analysis. The cytotoxicity of the ligands and complexes has been tested against a panel of various cancer cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide