Abstract

A set of seven hydroxycoumarin derivatives (1-7) were tested to evaluate their antioxidant properties. These molecules were selected on the basis of the number of hydroxyl groups and the presence of electron-donating and electron-withdrawing groups in their scaffolds. Electrochemical studies showed that oxidation process occurs at low potentials, especially with the catechol-containing coumarins. Electron spin resonance (ESR) experiments corroborated the formation of semiquinone radicals in all compounds. The antioxidant properties against peroxyl and hydroxyl radicals were evaluated using two different assays, namely oxygen radical antioxidant capacity (ORAC) and non-catalytic Fenton system by ESR measurements. Our results indicated that monohydroxycoumarin derivatives (1 and 2) displayed better ORAC values relative to the standard molecule Trolox. These values are comparable with known flavonoids such as quercetin and catechin. On the other hand, compounds bearing catechol and resorcinol groups, including derivative 4, gave high hydroxyl radical-scavenging properties. Antioxidant properties were further rationalized using density functional theory calculations. The theoretical results showed good trends among the obtained experimental data, calculated bonding dissociation enthalpy, highest occupied molecular orbital values, free energies of oxidation (Gox) and spin density distribution. Finally, in vitro studies revealed low toxicity for most of the coumarins studied. The cytoprotection assays in bovine aortic endothelial cells indicated that compounds 1 and 2 showed better protective properties against peroxynitrite and hydrogen peroxide-induced cell death than dihydroxycoumarin derivatives. Using confocal microscopy, we have observed intracellular compartmentalization. These results confirm that 1 or 2 would be a good target for future in vivo studies against oxidative stress. Copyright (c) 2013 John Wiley & Sons, Ltd.