Cytotoxicity of ruthenium-arene complexes containing B-ketoamine ligands

New ruthenium(II) arene derivatives (arene = p-cymene, benzene, hexamethylbenzene) containing beta-ketoamine ligands L' (HL' in general; in detail, HLph,ph = (4Z)-3-methyl-4-((phenylamino)(phenyl)methylene)-1-phenyl-1H-pyrazol-5(4H)-one, HLnaph,ph = (4Z)-3-methyl-4-((phenyamino)(naphthalen-2-yl)methylene)-1-phenyl-1H-pyrazol-5(4H)- one, HLet,ph = (4Z)-3-methyl-4-(1-(phenylamino)propylidene)-1-phenyl-1Hpyrazol-5(4H)-one) have been synthesized and characterized by spectroscopy (IR, ESI-MS, H-1 and C-13 NMR) and elemental analysis. The ligands in the anionic form coordinate ruthenium in a chelating kappa N-2,O-bidentate fashion, affording 1:1 derivatives of the formula [Ru(arene)(L')Cl]. Further reaction of [Ru(p-cymene)(L')Cl] with AgPF6 or PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) in methanol affords [Ru(p-cymene)(L')(CH3OH)] [PF6] and [Ru(p-cymene) (L')(PTA)]Cl, respectively. The solid-state structures of the ligand HLet,ph and complexes [Ru(p-cymene)(L-ph,L-ph)Cl] (1), [Ru(p-cymene)(L-naph,L-ph)Cl] (4), and [Ru(p-cymene)(L-et,L-ph)Cl] (7) have been determined by single-crystal X-ray diffraction. The antitumor activity of both the ligands and complexes has been evaluated against the human ovarian carcinoma cell line A2780 and its cisplatin-resistant equivalent A2780R, some of the complexes showing significant cytotoxicity toward the cisplatin-resistant cell line.