Synthesis, Structure, and Anticancer Activity of Arene-Ruthenium(II) Complexes with Acylpyrazolones Bearing Aliphatic Groups in the Acyl Moiety

A series of neutral ruthenium(II) arene complexes [(arene)Ru(Q(R))Cl] (arene = p-cymene (cym) or hexamethylbenzene (hmb)) containing 4-acyl-5-pyrazolonate Q(R) ligands with different electronic and steric substituents (R = 4-cyclohexyl, 4-stearoyl, or 4-adamantyl) and related ionic complexes [(arene)Ru(Q(R))(PTA)][PF6] (PTA = 1,3,5-triaza-7- phosphaadamantane) were synthesized and characterized by spectroscopy (IR, UVvis, ESI-MS, and H-1 and C-13 NMR), elemental analysis, X-ray crystallography, and density functional theory studies. The cytotoxicity of the proligands and metal complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against nontumorous human embryonic kidney (HEK293) cells. In general the cationic PTA-containing complexes are more cytotoxic than their neutral precursors with a chloride ligand in place of the PTA. Moreover, the complexes do not show cross-resistance and are essentially equally cytotoxic to both the A2780 and A2780cisR cell lines, although they only show limited selectivity toward the cancer cell lines.