Nitric oxide and free stable nitroxyl radicals in the mechanism of biological action of the spin-labeled compounds

A comparison of more important physical, chemical and biological properties of the nitric oxide (NO) and free stable nitroxyl radicals (nitroxides) on the base of their structural similarity is made in the article. The active moiety in the nitroxide molecule represents a sterically hindered nitric o xide. The mechanisms of biological action of the nitroxides and especially of their derivatives with antitumor agents from the groups of nitrogen must ards, nitrosoureas, aziridines and triazenes (spin-labeled compounds) is ex plained through the biological activities of sterically hindered NO. Simila rly to NO, nitroxides also can react with superoxide anion radical (O-2(-)) they possess superoxide dismutase (SOD) mimetic action. While the interact ion of NO with O-2(-) yields very toxic peroxynitrite (ONOO-), its formatio n is strongly limited in the presence of a nitroxide. It is known that the nitrosourea antitumor drugs, like lomustine (CCNU) and carmustine (BCNU), s howed high general toxicity, one of the reasons for that probability is the formation of NO, and subsequently of ONOO-, during their metabolism. The b iological investigations of the nitroxides showed their considerably lower general toxicity that could be explained with the SOD-mimetic action of the nitroxide present in their molecule. (C) 2001 Harcourt Publishers Ltd.