New Tumor-Inhibiting Metal Complexes. Chemistry and Antitumor Properties

Metals such as platinum, gold, ruthenium, titanium and tin can be a source of biologically active derivatives and, occasionally, become tools in the chemotherapy against different kinds of human tumors. The preclinical evaluation includes not only antitumor activity tests but also the investigation of the particular chemistry, the molecular targets within biological materials and the effect on the survival of a cell within its particular environment. These metals may form coordination compounds by binding ligands firmly or loosely, depending on the chemical nature of both the metal ion and the ligands. A loosely coordinated chloride ion or water molecule will exchange for a more nucleophilic biomolecule, commonly a nucleobase or a sulfur-containing amino acid side chain, and thereby infer a biological lesion. A metal ion complex may require an exchange of one or more ligands for water in order to become activated. All the firmly bound, conserved, ligands influence both target selection and reactivity of the metal ion. Following the important thesis of Collier and Krauss from the 30s ("The effect of a heavy metal on experimental murine cancer is not only due to the metal alone, but also to the structure of the compounds and the type of compound"), it should be emphasized that the efficacy of a metal complex against cancer is primarily related to the kind of its set of ligands and to the resulting substitution stability of the different bounded ligands. Under this aspect, two new tumor-inhibiting metal complexes will be discussed in this article, the ruthenium complex