Synthesis, electrochemical studies and evaluation of antioxidant and protective effects against lipid peroxidation of amide-derived lipoic acid

The detrimental effects of Reactive Oxygen Species (ROS), Reactive Nitrogen Species (RNS) and other reactive species, responsible, when in excess, for Oxidative Stress (OS), can be fought by the action of antioxidants such as lipoic acid (LA). LA exerts most of its effects at high micromolar concentrations. There is an up-raising interest in derivatives of LA, since molecular combinations (hybrids) obtained by coupling LA with a bioactive amino-substituted moiety may exhibit multifunctional activity. In the present study, amides from the reaction of LA with hydroxyl- and thiolated anilines were synthesized and evaluated toward their protective effects against lipid peroxidation and carbonyl stress. Three derivatives were obtained, being the methylthio derivative, LASCH3, reported for the first time in the literature. The protection against lipid peroxidation was evaluated by peroxyl radical-mediated lipid peroxidation based on a unilamellar soybean lecithin membrane model. Lipid peroxidation assays showed that all compounds protected the membrane, and that the phenol LA-OH had similar protective effects on membrane as Trolox, being more effective than its precursor, LA. IC50 value for LA-OH was obtained as well as its electrochemical profile in protic medium, together with pH effects, with evidence of two oxidation peaks, characteristic of its multifunctional characteristics, represented by phenolic and disulfide groups.