New polydentate Ru(III)-Salan complexes: Synthesis, characterization, anti-tumour activity and interaction with human serum proteins

Two new Ru(III) complexes bearing tetradentate N2O2 bis(aminophenolate) ligands (i.e. Salan-type ligands), were synthesized and characterized. The paramagnetism of the new [RuIII(Salan)Cl(PPh3)] (Salan = 4-methoxy/5-methoxy derivatives of 1,4-bis(salycilidene)cyclohexanediamine, PPh3 = triphenylphosphane) was proved by spectroscopic studies. These complexes exhibit a 4d5 low-spin distorted octahedral geometry. The anti-tumour activity of ligands and complexes was screened in vitro against A2780, MCF7 and MDAMB231 human cancer cell lines. Both ligands and complexes exhibit moderate to high cytotoxicity against all investigated cell lines, in some cases surpassing that of Cisplatin. Coordination to the Ru(III) center enhanced the cytotoxicity of each bis(aminophenolate) ligand by at least twofold.Binding of both Ru(III)-Salan complexes to human serum albumin is strong, as evaluated by steady-state and time-resolved fluorescence spectroscopy, suggesting that this protein might be a transport vehicle in the blood serum for these agents. The cytotoxicity of the protein-bound Ru(III)-Salan complex was assessed, as well as the effect of serum albumin binding on the activity of these complexes.These new Ru(III)-Salan are the first compounds of this class studied for anti-tumour proposes reported in the literature.

We report the first two Ru(III)-Salan complexes with anti-proliferative activity against A2780, MCF7 and MDAMB231 human cancer cell lines. IC50 values found for these compounds are of the same magnitude or surpass those found for cisplatin, depending on the cell line studied. Strong interaction with HSA assessed by fluorescence spectroscopy suggests that these potential drugs might be transported in the blood serum to target cells by albumin while retaining cytotoxicity.Figure optionsDownload as PowerPoint slideHighlights
► We synthesized and characterized the first Ru(III)-Salan complexes for anti-tumour application.
► These complexes are 3- to 7-fold more cytotoxic than cisplatin against MCF7 breast adenocarcinoma cells.
► A strong interaction with HSA suggests possible transport in the blood.
► The complex-albumin conjugates maintain cytotoxic activity against human cancer cells.