Influence of the Arene Ligand and the Leaving Group on the Anticancer Activity of (Thio)maltol Ruthenium(II)-(η6-Arene) Complexes

Maltol and its metal complexes have shown promising applications in medicinal chemistry. We report here the synthesis and characterization of Ru(eta(6)-arene)(halido) coordination compounds bearing maltol or thiomaltol ligands and studies on their behaviour in aqueous solution, their reactions with the DNA model guanosine 5'-monophosphate (5'-GMP) and their in vitro anticancer activity in human tumour cell lines. The compounds hydrolyze rapidly and quantitatively to the respective aqua species by exchange of the halido ligand. With pK(a) values of >8, such species would also be present in biological media and they proved reactive to 5'-GMP. The thiomaltol compounds show promising in vitro activity with IC50 values (50% inhibitory concentration) in the low micromolar range, whereas activity of the maltol complexes is marginal. Variation of the arene ligand (benzene, toluene, p-cymene or biphenyl) resulted only in minor changes in activity.