Antimetastatic properties and DNA interactions of the novel class of dimeric Ru(III) compounds [Na]2{trans-RuCl4(Me2SO)]2(µ-L)} (L = ditopic, non-chelating aromatic N-ligand)

A novel class of dianionic Ru(III) dimers of formula Na2[{trans-RuCl4(Me2SO)}2(μ-L)], with L=pyrazine (pyz, 1), pyrimidine (pym, 2), 4,4′-bipyridine (bipy, 3), and 1,2-bis(4-pyridine)ethane (etbipy, 4), was developed by us with the specific aim of assessing their antitumor properties. The dimers are in fact structurally related to the antimetastatic mononuclear compound (ImH)[trans-RuCl4(Me2SO)(Im)] (NAMI-A, Im=imidazole). Preliminary results concerning the antineoplastic activity of 1–4 against the murine MCa carcinoma model, a tumor which spontaneously metastasizes in the lungs, are reported. Similarly to what is normally observed with NAMI-A, the treatment with the dimeric complexes was scarcely effective against the growth of the primary tumor. However, dimers 1, 2, and 4 reduced very effectively the number and, in particular, the weight of lung metastases (to about 5% with respect to controls); in particular, Na2[{trans-RuCl4(Me2SO)}2(μ-etbipy)] (4) was as effective as NAMI-A in reducing the spontaneous metastases at a dosage which, in terms of moles of ruthenium, is about 3.5 times lower compared to that normally used for NAMI-A. Furthermore, in vitro tests showed that dimers 1–4 are capable of forming interstrand cross-links with linearized plasmidic DNA in a time-dependent manner. All the dimeric species are more active in inducing cross-links compared to NAMI-A, and the dimer bridged by the etbipy ligand (4) is the most effective among those tested.