Platinum Complexes with Bioactive Nitroxyl Radicals: Synthesis and Antitumor Properties

Nitroxyl radicals (NRs), which are sometimes called "organic nitrogen oxides” exhibit a wide range of biological activities, e.g., hemodynamic effect, protection against ionizing radiation, suppression of oxidative stress in different types of pathology (Soule et al., 2007; Wilcox, 2010). Already in early studies of the simplest NRs, their antitumor activity was demonstrated on a model tumor, leukemia La (Konovalova et al., 1964) and their cytotoxicity was shown for HeLa cells (Klimek, 1966). Subsequent studies included: 1) indepth studies of antitumor activity of simple NRs (TEMPOL, TEMPO), 2) trials of therapeutical efficiency of NRs used in combination with the clinically approved anticancer drugs, and 3) synthesis and studies of hybrid compounds with NRs covalently bound to anticancer pharmacophores. Recent studies have shown that simple nitroxyls affect the cell viability through a redox-mediated signaling and induce a multifactor cell death response, including oxidative damage, cell cycle arrest and apoptosis (Gariboldi et al., 1998; 2000; 2003; Suy et al., 2005).