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 oxide. The mechanisms of biological action of the nitroxides and especially of their derivatives with antitumor agents from the groups of nitrogen mustards, nitrosoureas, aziridines and triazenes (spin-labeled compounds) is explained through the biological activities of sterically hindered NO. Similarly to NO, nitroxides also can react with superoxide anion radical (O(2)(-)), they possess superoxide dismutase (SOD) mimetic action. While the interaction of NO with O(2)(-)yields very toxic peroxynitrite (ONOO(-)), its formation is strongly limited in the presence of a nitroxide. It is known that the nitrosourea antitumor drugs, like lomustine (CCNU) and carmustine (BCNU), showed high general toxicity, one of the reasons for that probability is the formation of NO, and subsequently of ONOO(-), during their metabolism. The biological 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.
Raikov
Z D
ZD
Department of Chemistry and Biochemistry, Thracian University, Medical Institute, 6000 Stara Zagora, Bulgaria.
Raikova
E T
ET
Atanasov
A T
AT
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism*
D000970:Antineoplastic Agents; D009589:Nitrogen Oxides; D013113:Spin Labels; D009569:Nitric Oxide; D013482:Superoxide Dismutase; C039900:nitroxyl