Cytotoxic double arene ruthenium metalla-cycles that overcome cisplatin resistance

Tetranuclear arene ruthenium complexes of the general formula {Ru-2(p-cymene)(2)(mu(4)-L)}(2)(mu(4)-tpom) (tpom = tetrakis(4-pyridyloxymethylene)methane) were obtained from the corresponding dinuclear arene ruthenium complexes [Ru-2(p-cymene)(2)(m(4)-L)Cl-2] (L = diethyl-1,2-diazenedicarboxylato (dadc), oxalato (oxa), bis(2-hydroxyethyl)oxamidato (bho), bis{2-(2-hydroxyethoxy)ethyl}ethanediamidato (bhe), 2,5-dioxido-1,4-benzoquinonato (dobq), 2,5-dihydroxy-3-phenyl-1,4-benzoquinonato (dhpb), 2,5-dibromo-1,4-benzoquinonato (dBrbq), 2,5-dioxido-3-undecyl-1,4-benzoquinonato (dubq), 2,5-dihydroxy-3,6-diphenyl-1,4-benzoquinonato (dhdb), 2,5-dihydroxy-3,6-(3,5-dimethylphenyl)-1,4-benzoquinonato (dhdm), 5,8-dioxido-1,4-naphtoquinonato (donq)) by reaction with the tetradentate tpom ligand and silver trifluoromethanesulfonate. The antiproliferative activity of the tetranuclear complexes was evaluated on cancerous (A2780 and A2780cisR) and non-cancerous (HEK293) cell lines, showing in most cases cancer cell selectivity and, in some cases, low micromolar cytotoxicities (similar to 1 mu M) against a cancer cell line that has acquired resistance to cisplatin. (C) 2015 Elsevier B.V. All rights reserved.