Selected hydroxycoumarins as antioxidants in cells: physicochemical and reactive oxygen species scavenging studies

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 electronwithdrawing 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 (ΔG ox ) 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.

Evaluation of Trypanocidal and Antioxidant Activities of a Selected Series of 3-amidocoumarins

“…The electrochemical oxidation of the substituted 3-amidocoumarins was performed under the same conditions as for the CV but using N-tert-butyl-α-phenylnitrone (PBN) as a spin trapping. This trap allows the detection of centred carbon and oxygen radicals, increasing their half-life [28]. For all compounds, one hyperfine pattern of six lines was obtained ( Fig.…”

Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study

“…Available literature data indicate that hydrophilic coumarin derivatives show a positive effect in preventing, compensating, and removing ROS in the aqueous (cytosolic) compartment of the cell [14,15]. The reaction mechanism between coumarin and HO • can be complex, as several products can be formed [16].…”

The antioxidant activity of 4‐hydroxycoumarin derivatives and some sulfured analogs

“…This failure requires an urgency request for the designation of new chemical entities with strong radical scavenging activity. Over the past two decades, there have been an increasing number of publications on the antioxidant activities of natural or synthetic coumarins …”