Mechanism of biochemical action of substituted 4-Methylbenzopyran-2-ones. Part 5: Pulse radiolysis studies on the antioxidant action of 7,8-diacetoxy-4-methylcoumarin (original) (raw)
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Journal of Physical Organic Chemistry, 2019
In this work, the experimental and theoretical study on the primary and secondary antioxidant activities of three hydroxy-4-methylcoumarins were carried out. According to the experimental results obtained in the TEAC test employing ABTS, DPPH and galvinoxyl radicals, coumarin with the most important radical scavenging activity was 7,8-dihydroxy-4-methylcoumarin (HMD), even observing a radical scavenging activity greater than that demonstrated by the Trolox antioxidant. The theoretical results on primary antioxidant capability shown that the HMD has a good radical scavenging activity in lipid media when compared to other molecules with known antioxidant activity. It was also highlighted that HMD showed an excellent radical scavenging capability in aqueous media considering the physiological pH, the results indicated that it even has a more important radical scavenging capability than others coumarins that are considered excellent antioxidants. Hence, HMD showed a great versatility to stabilize different kinds of important biological radicals, in these results were highlighted their great antioxidant activity. In addition to the previous results, the secondary antioxidant activity was studied, the results showed that HMD could inhibit the reduction of the copper and in this way avoid the Haber-Weiss reactions, which leads to the increase of the hydroxyl radical concentration, and then, to oxidative stress. Therefore, this study shows that the HMD is able to stabilize the radicals in the primary antioxidant activity and avoid the generation of radicals through the Fenton reaction in the secondary antioxidant activity.
Biochimie, 2017
The aim of this study is to determine, and to compare the protective effects of eight 4-methylcoumarins and four related compounds as radical scavengers and chain-breaking antioxidants. The main kinetic parameters of their radical scavenging activity (as % RSA, stoichiometry, n, and rate constants of reaction with DPPH radical, k RSA) and of chain breaking antioxidant activity (as antioxidant efficiency, PF and reactivity, ID), have been determined and discussed. The RSA study has been conducted at physiological temperature (37 С) towards DPPH radical and the tested compounds are separated into three main groups: with strong activity (% RSA > 40%); with moderate activity (20% < % RSA > 40%) and with weak activity (% RSA < 20%). Chain-breaking antioxidant activities of the studied compounds have been evaluated during bulk phase lipid (triacylglycerols of sunflower oil, TGSO) autoxidation at 80 C. All results obtained are compared with those for standard and known inhibitors of oxidation processes, e.g. caffeic and p-coumaric acids, a-tocopherol and butylated hydroxytoluene (BHT). On the basis of a comparative analysis with standard antioxidants, the differences in the radical scavenging and antioxidant abilities of the studied compounds have been discussed and reaction mechanisms proposed. All structures are optimized at UB3LYP/6-31 þ G(d,p) level in gas phase and in acetone solution to study the solvation effects.
Antioxidant activity of 4-methylcoumarins
Journal of Pharmacy and Pharmacology, 2007
Polyphenolic coumarins are known to act as antioxidants in biological systems, but it is difficult to distinguish their antioxidant activity from the many other effects they produce in cells. We have determined the radical scavenging capacity of 22 structurally related natural and synthetic 4-methylcoumarins, by measuring their reaction with radicals, galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl, using electron paramagnetic resonance spectroscopy. Efficient antioxidant activity of 4-methylcoumarins in cells was verified using the DCF fluorescent probe assay for determination of intracellular reactive oxygen species levels. As expected, the o-dihydroxysubstituted coumarins were found to be excellent radical scavengers and better than the m-dihydroxysubstituted or monohydroxysubstituted analogues, but surprisingly the corresponding o-diacetoxy derivatives also turned out to be good scavengers, even in the absence of an esterase. Another unexpected result was that the anti-oxidant efficiency of 4-methylcoumarins could be modulated by introducing an ethoxycarbonyl-ethyl substituent at the C-3 position; this effect cannot be explained by simple electron donating/withdrawing properties. Coumarin concentrations of 10 μm or less were used in all experiments, corresponding to the levels relevant for therapeutic purposes. Considering that 4-methylcoumarins, in contrast to many other coumarins, are not metabolized to toxic epoxide intermediates, these results indicate promising new strategies for the design of non-toxic antioxidant coumarin-based drugs.
Journal of Physical Organic Chemistry, 2013
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.
Antioxidant properties of 4-methylcoumarins in in vitro cell-free systems
Biochimie, 2010
a b s t r a c t 4-Methylcoumarins that possess two hydroxyl groups ortho to each other in the benzenoid ring have shown to have excellent antioxidant and radical-scavenging properties in different experimental models. Furthermore, they cannot be metabolized by the liver P450 monoxygenases and thus cannot form 3,4-coumarin epoxides, which are believed to be mutagenic. Herein, we present a study on the structure activity relationship of eight synthetic 4-methylcoumarins, carried out by employing a series of different chemical cell-free tests. These compounds were tested by means of three assays involving one redox reaction with the oxidant (DPPH assay, ABTS þ assay and FRAP). Other assays were employed to evaluate the antioxidant properties of the coumarins under investigation against NO, O 2 À and HClO, which are some of the major reactive oxygen and nitrogen species causing damage in the human body. Finally, we have measured the protective capacity of these coumarins against the oxidative damage in a simple biomimetic model of phospholipid membranes. Our results confirm the good antioxidant activity of the 7,8-hydroxy-4-methylcoumarins. In general, their activity is not significantly affected by the introduction of an ethoxycarbonylmethyl or an ethoxycarbonylethyl moiety at the C3 position. A discrete antioxidant activity is retained also by the 7,8-diacetoxy-4-methylcoumarins, although they are less efficient than the corresponding 7,8-dihydroxy compounds. Furthermore, as demonstrated in the brine shrimp toxicity test, none of the tested coumarins significantly affect the larvae viability. Two of the 4-methylcoumarins (7,8-dihydroxy-4-methylcoumarin and 7,8-dihydroxy-3-ethoxycarbonylethyl-4-methylcoumarin), very interestingly, showed strong scavenging activities against the superoxide anion and were also very effective in protecting the lipid bilayer against peroxidation. On the basis of these findings, these 4methylcoumarins may be considered as potential therapeutic candidates for pathological conditions characterized by free radical overproduction.
Biochimie, 2010
The antioxidant activity of eight synthetic 4-methylcoumarins was systematically studied. The antioxidant capacity was measured using: (i) a competition kinetic test, to measure the relative capacity to quench peroxyl radical; (ii) the in vitro oxidative modification of human low-density lipoprotein, initiated by AAPH or catalyzed by copper. In both models, the ortho-OH substitutes were found to be better antioxidant than the meta one. The most efficient antioxidant was the 7,8-dihydroxy-4-methylcoumarin and the corresponding diacetoxy-substituted was unexpectedly a good antioxidant. Finally, the presence of an ethoxycarbonylethyl substituent at the C-3 position increased the antioxidant capacity of both 7,8-dihydroxy-4-methylcoumarin and 7,8-diacetoxy-4-methylcoumarin.
Food Chemistry, 2012
Continuing our research on oxidation reactions of 4-methylcoumarins (4-methyl-2H-1-benzopyran-2ones), this study presents evaluation of the antioxidant activity of 23 4-methylcoumarin derivatives, using different spectrophotometric and spectrofluorimetric radical testing methods. All studied compounds showed activity comparable to Trolox, an already known antioxidant, which is used as a standard in most testing methods. Observations from the study were made with regard to structural features that regulated the behaviour of the compounds. This paper extends our knowledge of the range of valuable biological activities and possible roles in medicinal therapy associated with this group of compounds.