The efficacy of monohydroxamates as free radical scavenging agents compared with di- and trihydroxamates.
Desferrioxamine, the therapeutic iron chelator, is limited in its usage by its short half-life in plasma and lack of oral activity, its side-effects and its slow penetration into cells. Several studies have emerged recently demonstrating the ability of this trihydroxamate compound to act as a radical scavenger, in addition to and independently of its iron-chelating properties. These include the interaction of desferrioxamine with the superoxide radical and ferryl myoglobin radical, as well as its action as a chain-breaking antioxidant in peroxidizing erythrocyte membranes. We have synthesized recently a series of monohydroxamate compounds and investigated their efficacy as radical scavenging antioxidants in comparison with desferrioxamine and rhodotorulic acid, a naturally occurring dihydroxamate compound. The results show that the relative rates of reaction of these hydroxamate derivatives with ferryl myoglobin are N-methyl-N-hexanoyl hydroxylamine > N-methyl-N-benzoyl hydroxylamine > N-methyl-N-acetyl hydroxylamine > desferrioxamine > rhodotorulic acid > N-methyl-N-butyryl hydroxylamine.
Green
E S
ES
Division of Biochemistry, UMDS, London, U.K.
Evans
H
H
Rice-Evans
P
P
Davies
M J
MJ
Salah
N
N
Rice-Evans
C
C
D003676:Deferoxamine / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000737:chemistry; D016166:Free Radical Scavengers; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D006898:Hydroxylamines / Q000737:chemistry; D015227:Lipid Peroxidation; D008563:Membrane Lipids / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry; D013053:Spectrophotometry
D016166:Free Radical Scavengers; D006877:Hydroxamic Acids; D006898:Hydroxylamines; D008563:Membrane Lipids; D010879:Piperazines; D003855:Deoxyribose; C003305:rhodotorulic acid; D003676:Deferoxamine