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 gt 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 gt 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.