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

A novel class of dianionic Ru(III) dimers of formula Na-2[trans-RuCl4(Me2SO )}(2)(mu-L)], With L = pyrazine (pyz, 1), pyrimidine (pym, 2), 4,4'-bipyrid ine (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 dime rs are in bet structurally related to the antimetastatic mononuclear compou nd (ImH) [trans-RuCl4(Me2SO) (Im)] (NAMI-A, Im = imidazole). Preliminary re sults 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 treatmen t with the dimeric complexes was scarcely effective against the growth of t he 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, Na-2[(transRuCl(4)(Me2SO)} (2)(mu-etbi py)] (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 sho wed that dimers 1-4 are capable of forming interstrand cross-links with lin earized plasmidic DNA in a time-dependent manner. All the dimeric species a re more active in inducing cross-links compared to NAMI-A, and the dimer br idged by the etbipy ligand (4) is the most effective among those tested. (C ) 2000 Elsevier Science Inc. All rights reserved.