Ruthenium arene complexes with mono-carbonyl analogues of curcumin as pendant or bridging ligands: Synthesis, anti-cancer activity and interaction with quadruplex DNA

Abstract Four ruthenium(II) arene complexes containing mono-carbonyl analogues of curcumin (MAC) functioning as pendant or bridging ligands as well as chlorido ancillary ligands have been synthesized and structurally characterized by IR and 1H NMR spectroscopies, ESI mass spectrometry and elemental analysis. Anti-proliferative activity of the complexes determined on MOLT-4 human leukemia cells revealed good to moderate activity. Two of the compounds, 3b and 4b, both of which incorporated cyclohexanone as part of the MAC structural motif, displayed potency comparable to cisplatin. In intercalative binding studies, while the organic MACs did not display any interaction with quadruplex DNA, the ruthenium complexes were found to be able to stabilize quadruplex DNA, with 3b and 4b displaying the greatest selectivity for HTelo over c-myc. Compound 4b, in which the MAC ligand is bridged by two organoruthenium centres, bound to HTelo more tightly than 3b, in which the MAC functions as a pendant ligand towards a single ruthenium arene core. These results suggest that minor changes to the structural motif of the MAC ligand, as well as the presence of the ruthenium arene moiety play an important role in achieving selective quadruplex DNA stabilization.