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(QR)­Cl]
(arene = p-cymene (cym) or hexamethylbenzene (hmb))
containing 4-acyl-5-pyrazolonate QR ligands with different
electronic and steric substituents (R = 4-cyclohexyl, 4-stearoyl,
or 4-adamantyl) and related ionic complexes [(arene)­Ru­(QR)­(PTA)]­[PF6] (PTA = 1,3,5-triaza-7-phosphaadamantane)
were synthesized and characterized by spectroscopy (IR, UV–vis,
ESI-MS, and 1H and 13C 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.