Antimetastatic properties and DNA interactions of the novel class of dimeric Ru(III) compounds Na2[[trans-RuCl4(Me2SO)]2(mu-L)] (L = ditopic, non-chelating aromatic N-ligand). A preliminary investigation.

Abstract

A novel class of dianionic Ru(III) dimers of formula Na2[[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 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(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.

• Authors: E Alessio, E Iengo, S Zorzet, A Bergamo, M Coluccia, A Boccarelli, G Sava
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 79 Issue 1-4 Pg. 173-7 (Apr 2000) ISSN: 0162-0134 [Print] United States
• PMID: 10830863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ligands
• Organometallic Compounds
• Ruthenium
• DNA

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, therapeutic use)
• DNA (chemistry)
• Dimerization
• Female
• Ligands
• Lung Neoplasms (drug therapy, pathology, secondary)
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred CBA
• Organometallic Compounds (chemical synthesis, chemistry, therapeutic use)
• Ruthenium