Metal complexes of ruthenium: antineoplastic properties and perspectives

Octahedral ruthenium(III) and ruthenium(II) complexes show antineoplastic properties on a number of experimental tumors. Tetraammine-, pentaammine-, heterocycle-, and dimethylsulfoxide-coordinated ruthenium complexes have shown high affinity for nitrogen donor ligands in vitro and as a result exhibit various degrees of biological activities including antitumor action in vivo. The chemical behavior of ruthenium(III) complexes indicates the possibility of opening a window of selective toxicity, in practice lacking in the chemotherapeutic approach to neoplastic diseases. Ruthenium ions may accumulate in tumor tissues via a mechanism mediated by transferrin transport. Moreover, binding of ruthenium to DNA is several times higher in its reduced ruthenium(II) form and the reduction from ruthenium(III) prodrugs to the more toxic ruthenium(II) compounds is particularly efficient in tumor hypoxic environments. Correspondingly, solid tumors appear to be more susceptible than those of the lymphoproliferative type. In particular, tumors of the colorectal region and lung tumors (primary or metastatic), which are generally associated with a bad prognosis, have given interesting responses in experimental models, indicating these tumors as preferential targets for the development of ruthenium anticancer drugs.