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

Abstract

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, H-1 and C-13 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 mu M), 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 mu M). 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 mu M versus IC50 > 120 mu M for cisplatin). In parallel, primary fibroblasts-MRC-5 were remarkably less affected by these compounds. (C) 2013 Elsevier B. V. All rights reserved.