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

摘要

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'-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 bet 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, Na-2[(transRuCl(4)(Me2SO)} (2)(mu-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. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 17]