[Show abstract][Hide abstract] 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.
Full-text · Article · Oct 2013 · Journal of Physical Organic Chemistry
[Show abstract][Hide abstract] ABSTRACT: A series of novel hydroxy-coumarin-chalcone hybrid compounds 2a-i has been synthesized employing a simple and efficient methodology. An electrochemical characterization using cyclic voltammetry and ESR spectroscopy were carried out in order to characterize the oxidation mechanism for the target compounds. The antioxidant capacity and reactivity were determined by ORAC and ESR assays, respectively. Biological assays were assessed in order to evaluate the cytotoxicity and cytoprotection capacity against ROS/RNS on BAEC. The results revealed that all tested compounds present ORAC values much higher than other well-known antioxidant compounds such as quercetin and catechin. Compound 2e showed the highest ORAC value (14.1) and also presented low oxidation potential, good scavenging capacity against hydroxyl radicals, low cytotoxicity and high cytoprotective activity. Key words: coumarin, chalcone, Knoevenagel reaction, electrochemical study, antioxidant activity, cytotoxicity, cytoprotection, ADME.
[Show abstract][Hide abstract] ABSTRACT: The study of antioxidants and radicals has always been a complex task due to the special characteristics of these species such as reactions at low concentrations and short half-lives. Current techniques do not always produce good results and in some cases they can only be applied in chemical models. From this point of view, the development of electron spin resonance (ESR) has allowed the study of the antioxidant capacity of a wide variety of compounds and the detection of radicals in the reactions in which they are involved. The DPPH technique allows only the study of antioxidants in pure chemical models. The ORAC-ESR assay, based on the spin trapping technique, emerges as an interesting tool for identifying and quantifying the antioxidant capacity of different samples. Furthermore, the spin trapping technique allows us to characterize radicals in in vivo/ex vivo models. The present review discusses the current available techniques associated with ESR for the study of antioxidants and radical species.
Full-text · Article · Jun 2013 · Current Medicinal Chemistry
[Show abstract][Hide abstract] ABSTRACT: In the present work we synthesized a series of hydroxy-3-arylcoumarins (compounds 1-9), some of them previously described as MAO-B selective inhibitors, with the aim of evaluating their antioxidant properties. Theoretical evaluation of ADME properties of all the derivatives was also carried out. From the ORAC-FL, ESR and CV data it was concluded that these derivatives are very good antioxidants, with a very interesting hydroxyl, DPPH and superoxide radicals scavenging profiles. In particular compound 9 is the most active and effective antioxidant of the series (ORAC-FL=13.5, capacity of scavenging hydroxyl radicals=100%, capacity of scavenging DPPH radicals=65.9% and capacity of scavenging superoxide radicals=71.5%). Kinetics profile for protection fluorescein probe against peroxyl radicals by addition of antioxidant molecule 9 was also performed. Therefore, it can operate as a potential candidate for preventing or minimizing the free radicals overproduction in oxidative-stress related diseases.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to characterize the complex between mangiferin (MGN) with β-cyclodextrin (β-CD) obtained through the co-evaporation method using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FT-IR), as well as to verify the antioxidant activity of this complex by means of radical scavenging activity toward 2,2′-diphenyl-1-picrylhydrazyl radical (RSA-DPPH), with additional analysis of solvent effects, and Oxygen Radical Antioxidant Capacity-Fluorescein (ORAC-FL) assays. The protective effects of MGN and the MGN:β-CD complex against peroxyl radical-initiated membrane lipid peroxidation were also evaluated. The analysis of the solvent effects in the DPPH method demonstrated that at amounts of organic solvents lower than the ratio 50:50 (methanol–water or ethanol–water) there is a drawback, due to the hydrophobic nature of DPPH and should not be used. The antioxidant activity of the MGN:β-CD complex was higher than in its free form, as seen by both methods. The RSA-DPPH value was twofold larger for the complex while the ORAC-FL value was fifteenfold larger. Lipid peroxidation assays showed that the MGN:β-CD complex has a protective effect on the membrane that is as effective as the positive control (Trolox).
[Show abstract][Hide abstract] ABSTRACT: Hypochlorite is a strong oxidant able to induce deleterious effects in biological systems. The goal of this work was to investigate the use of PGR and PYR as probes in assays aimed at evaluating antioxidant activities towards hypochorite and apply it to plant extracts employed in Chilean folk medicine. The consumption of PGR and PYR was evaluated from the decrease in the visible absorbance and fluorescence intensity, respectively. Total phenolic content was determined by the Folin Ciocalteau assay. PGR and PYR react with hypochlorite with different kinetics, being considerably faster the consumption of PGR. Different stoichiometric values were also determined: 0.7 molecules of PGR and 0.33 molecules of PYR were bleached per each molecule of added hypochlorite. Both probes were protected by antioxidants, but the rate of PGR bleaching was too fast to perform a kinetic analysis. For PYR, the protection took place without changes in its initial consumption rate, suggesting a competition between the dye and the antioxidant for hypochlorite. Plant extracts protected PYR giving a PYR-HOCl index that follows the order: Fuchsia magellanica » Marrubium vulgare » Tagetes minuta > Chenopodium ambrosoides » Satureja montana > Thymus praecox. Based on both the kinetic data and the protection afforded by pure antioxidants, we selected PYR as the best probe. The proposed methodology allows evaluating an antioxidant capacity index of plant extracts related to the reactivity of the samples towards hypochlorite.
[Show abstract][Hide abstract] ABSTRACT: A new nitrooxoisoaporphine derivative was synthetized and characterized by cyclic voltammetry and electron spin resonance. Its aqueous solubility was improved by complexes formation with β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin and (2-hydroxypropyl)-β-cyclodextrin. In order to assess the inclusion degree reached by nitrooxoisoaporphine in cyclodextris cavity, the stability constants of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-A(L) diagram. Moreover, electrochemical studies were carried out, where the observed change in the EPC value indicated a lower feasibility of the nitro group reduction. Additionally, a detailed spatial configuration is proposed for inclusion of derivate within the cyclodextrins cavity by 2D NMR techniques. Finally, these results are further interpreted by means of molecular modeling studies. Thus, theoretical results are in complete agreement with the experimental data.
No preview · Article · Oct 2012 · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy
[Show abstract][Hide abstract] ABSTRACT: In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. We have used the 4-hydroxycoumarin moiety (compound 1) as the molecular template for the synthesis of compounds 2-7. These derivates have shown moderate trypanocidal activity. However they have been proved to be good antioxidants. In particular compound 7 is the most active antioxidant and it is, therefore, a potential candidate for a successful employment in conditions characterized by free radicals overproduction.
[Show abstract][Hide abstract] ABSTRACT: The present work aims to investigate the electrochemical behavior of nine naphthoquinones, in aprotic and protic media. The reduction mechanism of the quinones in aprotic medium was proposed, with involvement of anion radical species, confirmed by performing in-situ Electrochemical-Electron Spin Resonance (E-ESR) experiments. Theoretical calculations using DFT method (U)B3LYP/6-31 were developed in order to rationalize the experimental hyperfine coupling constants. The results were in good agreement with the experimental data when solvent effects were included in the DFT models.
No preview · Article · Jul 2012 · International journal of electrochemical science
[Show abstract][Hide abstract] ABSTRACT: Phenolic compounds are bioactive substances widely distributed in the vegetable kingdom. They act as natural antioxidants, and their presence contributes to the color, flavor and aroma of food. This group of micronutrients is composed of one or more aromatic benzene rings with one or more hydroxyl groups and their redox properties are related with their chemical structure characteristics. The knowledge of their redox potentials may help the food industry, because when phenolic compounds are oxidized they could affect the quality of the wines, beers, grape juices, etc.
Coumarins are a large family of compounds, of natural and synthetic origin, that show important biological activities. Therefore, they occupy an important place in the study of natural products and synthetic organic chemistry. Recent studies pay special attention to their antioxidative, anticarcinogenic and enzymatic inhibition properties. Their preparation, and the versatility of the synthetic methodology, allowed us obtaining a wide family of compounds with substituent in different positions in the molecule. The election of these derivatives has considered the later pharmacological evaluation.
The investigation of the properties of these compounds, the study of the structural pattern and the elucidation of their biological role is of great interest for further development of coumarin-like antioxidant drugs. The electrochemical behaviour of a group of differently substituted hydroxycoumarins was investigated using cyclic, differential pulse and square wave voltammetry, in aqueous media at a glassy carbon electrode over the whole pH range. The antioxidant reactivity and capacity were also evaluated through a competition assay with hydroxyl radical (OH•) and ORAC-FL methodology. Number and positions of the hydroxyl groups were important factors in the antioxidant activities against peroxyl and hydroxyl radicals of the coumarin derivatives.
[Show abstract][Hide abstract] ABSTRACT: Four different 5-nitroindazole derivatives (1–4) and its inclusion with Heptakis(2,6-di-O-methyl)-β-cyclodextrin (DMβCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-AL diagram. Also electrochemical studies were carried out, where the observed change in the EPC value indicated a lower feasibility of the nitro group reduction. The same behavior was observed in the ESR studies. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.
[Show abstract][Hide abstract] ABSTRACT: Properties of inclusion complexes between morin (M) and beta-cyclodextrin (betaCD), 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and Heptakis (2,6-O-di methyl) beta-cyclodextrin (DMbetaCD) such as aqueous solubility and the association constants of this complex have been determined. The water solubility of morin was increased by inclusion with cyclodextrins. The phase-solubility diagrams drawn from UV spectral measurements are of the A(L)-type. Also ORAC(FL) studies were done. An increase in the antioxidant reactivity is observed when morin form inclusion complex with the three cyclodextrin studied. Finally, thermodynamics studies of cyclodextrin complexes indicated that for DMbetaCD the inclusion is primarily enthalpy-driven process meanwhile betaCD and HPbetaCD are entropy-driven processes. This is corroborated by the different inclusion geometries obtained by 2D-NMR.
Full-text · Article · Nov 2008 · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy