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physicochemical properties, interaction with DNA, cytotoxicity *in vitro* and antitumor activity *in vivo* were studied. A limited correlation was found between the ability of new complexes to form adducts with DNA, thermal stability of these adducts and antitumor activity of the complexes. PNCs are characterized by features that distinguish them from platinum complexes with usual alkylamines. An antagonism of platinum and nitroxyl pharmacophore was observed in cell culture. As compared to cisplatin or satraplatin, structurally close nitroxyl derivatives are approximately 10 times less cytotoxic. This may be explained by a moderate inhibition of p53-dependent apoptosis due to the antioxidant properties of nitroxyl radicals. These *in vitro* findings do not correlate with *in vivo* data, and antitumor activities of some PNCs and cisplatin are approximately the same. The relatively slow development of resistance to PNCs and the presence of synergy for the combinations of PNCs and cisplatin imply the differences in the mechanism of antitumor action of cisplatin and PNCs. Due to antioxidant properties (Sen' et al., 2000), nitroxyls in PNCs may ameliorate side effects typical for cisplatin, such as nephrotoxicity and neurotoxicity. For example, nitroxyl derivative of daunorubicin, ruboxyl, has virtually no cardiotoxicity that limits therapeutical doses of the parental compound (Emanuel & Konovalova, 1992). Reduced side effects, in turn, contribute to the better survival and, as a result, the higher efficacy of tumor chemotherapy *in vivo*. Our and literature data show that nitroxyls are promising modulators of the activity of anticancer agents and, as such, could be approved


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**Chapter 15** 
