Anticancer ruthenium(II) tris(pyrazolyl)methane complexes with bioactive co-ligands.

In comparison with Ru II -arene compounds, the medicinal potential of homologous Ru II -tpm compounds [tpm = tris(pyrazolyl)methane] is underexplored. Pyridine, 4-pyridinemethanol and four functionalized pyridines, synthesized from the esterification of 4-pyridinemethanol with bioactive carboxylic acids ( i.e. , ethacrynic acid, ibuprofen, flurbiprofen and naproxen), react with the precursor [RuCl(κ 3 -tpm)(PPh 3 ) 2 ]Cl (1) to afford [RuCl(κ 3 -tpm)(PPh 3 )(L)]Cl (2-7, L = pyridine ligand), in 78-91% yields. All products were fully characterized by HR-ESI mass spectrometry, IR and multinuclear NMR spectroscopy and the solid-state structures of two of the complexes, i.e. where L = pyridine and 4-pyridinemethanol, were ascertained by single crystal X-ray diffraction. The {Ru-tpm-PPh 3 } assembly is stable in D 2 O and in biological medium (DMEM) at 37 °C, with a tendency to slowly dissociate the pyridine ligand. The antiproliferative activity of the complexes was assessed on the cancerous A2780 and A2780cisR cell lines, and the nontumoral HEK 293T cell line; moreover inhibition assays were carried out on the complexes towards COX-2 and GSTP1 enzymes.