Structural Concept of Nitroxide As a Lipid Peroxidation Inhibitor

Nitroxides have antioxidative activities toward lipid peroxidation, but the influence of steric factors is not known. We synthesized alkyl-substituted nitroxides at the α-position of the N–O moiety to enhance lipophilicity and the bulk effect. There was good correlation between the IC50 and lipophilicity (log P o/w) of nitroxides with use of the thiobarbituric acid-reactive substances (TBARS) assay. Furthermore, an inhibitory effect on the TBARS assay was dependent upon the number and length of alkyl groups, though nitroxides had almost identical lipophilicity.