Arene ruthenium complexes with phosphinoferrocene amino acid conjugates: Synthesis, characterization and cytotoxicity

A series of heterodinuclear p-cymene ruthenium ferrocene complexes, [(eta(6)-p-MeC6H4Pri)RuCl2(Ph(2)Pfc-CONHRCO2Me-kappa P)] (R = (S)-Me: 6, R = (S)-CHMe2: 7, R = (S)-CH2OMe: 8, R = (S)-CH2SMe: 9, R = (S)-CH2CH2CO2Me: 10) have been synthesized from p-cymene ruthenium dichloride dimer and phosphinoferrocene ligands bearing carboxamide substituents derived from amino acids, Ph(2)PfcCONHRCO(2)Me (R = (S)-Me: 1, R = (S)-CHMe2: 2, R = (S)-CH2OMe: 3, R = (S)-CH2SMe: 4, R = (S)-CH2CH2CO2Me: 5, fc = ferrocene-1,1'-diyl). All new compounds, 3-10, were fully characterized by elemental analysis, multinuclear NMR and IR spectroscopy and electrospray ionisation mass spectrometry, and their electrochemical properties were studied by cyclic voltammetry at a platinum disc electrode. The cytotoxicity of 6-10 was studied on human ovarian cancer cells. The related glycine derivatives [(eta(6)-arene) RuCl2(Ph(2)PfcCONHCH(2)CO(2)Me-kappa P)] (arene = C6H6: 11a, arene = p-MeC6H4Pri: 11b, arene = C6Me6: 11c), [(eta(6)-arene)RuCl(MeCN)(Ph(2)PfcCONHCH(2)CO(2)Me-kappa P)][PF6] (arene = C6H6: 12a, arene = p-MeC6H4Pri: 12b, arene = C6Me6: 12c), [(eta(6)-arene)Ru(MeCN)(2)(Ph(2)PfcCONHCH(2)CO(2)Me-kappa P)]PF6 (arene = C6H6: 13a, arene = p-MeC6H4Pri: 13b, arene = C6Me6: 13c) and [(eta(6)-p-MeC6H4Pri)RuCl2(Ph(2)PfcCONHCH(2)CONH(2)-kappa P)] (14), which we reported recently, were also included in the cytotoxicity study. The arene ruthenium ferrocene complexes show moderate to good in vitro anticancer activity towards human ovarian cancer cells, the IC50 values of the most active derivative 13c being 4.1 +/- 0.8 mu M for the A2780 cell line and 6.9 +/- 0.01 mu M for the cisplatin-resistant derivative A2780cisR. (C) 2012 Elsevier B.V. All rights reserved.