N-acyl dehydroalanines scavenge oxygen radicals and inhibit in vitro free radical mediated processes

Abstract

N-substituted dehydroalanines react with and scavenge oxygen radicals. One of those compounds, the para-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-5, inhibits the reduction of ferricytochrome c by superoxide anion (O2-.). It can also inhibit the oxidation of linolenic acid, another chemical process, which is mediated by hydroxyl radical (HO.). Furthermore, microsomal lipid peroxidation induced by iron salts was also inhibited by AD 5, but with a different degree of efficacy. In fact, lipid peroxidation initiated by a ferrous-oxygen complex (as in iron/NADPH-dependent peroxidation) was inhibited by AD 5 in a range of concentration of 2-4 mM. On the contrary, iron/NADPH-independent lipid peroxidation, where alkoxy radicals (RO.) have principally been involved, was inhibited in a range of concentration of 6-10 mM. The ESR studies by using the spin trapping agent DMPO, show that AD-5 reacts with HO. with a second order constant of 2.8 X 10(9)-4.5 X 10(9) M-1 s-1.