Cytotoxicity of Ruthenium–Arene Complexes Containing β‑Ketoamine Ligands

New ruthenium­(II) arene derivatives (arene = p-cymene, benzene, hexamethylbenzene) containing β-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-1H-pyrazol-5­(4H)-one) have been synthesized and characterized by spectroscopy (IR, ESI-MS, 1H and 13C NMR) and elemental analysis. The ligands in the anionic form coordinate ruthenium in a chelating κ2N,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)­(Lph,ph)­Cl] (1), [Ru­(p-cymene)­(Lnaph,ph)­Cl] (4), and [Ru­(p-cymene)­(Let,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.