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.