Interactions of a series of coumarins with reactive oxygen species: Scavenging of superoxide, hypochlorous acid and hydroxyl radicals

doi:10.1016/0006-2952(92)90002-Z

Biochemical Pharmacology

Volume 44, Issue 2, 22 July 1992, Pages 205-214

https://doi.org/10.1016/0006-2952(92)90002-Z Get rights and content

Abstract

Sixteen plant-derived or synthetic coumarins with various hydroxyl and other substitutions were tested for their ability to inhibit lipid peroxidation and to scavenge hydroxyl radicals, superoxide radicals and hypochlorous acid. Seven unsubstituted or monosubstituted coumarins were essentially inactive in all tests except for ability to scavenge OH with rate constants ⪸1 × 10⁹ M⁻¹. sec⁻¹. Of the remaining nine, six containing dihydroxy substitutions were effective inhibitors of Fe³⁺-ascorbate-dependent microsomal lipid peroxidation $(ic_{50} < 20 μ M)$ , with ortho-dihydroxy + one additional substitution optimal $(ic_{50} < 10 μ M)$ . ortho-Dihydroxylated coumarins were pro-oxidant (enhanced OH^. generation) in the Fe³⁺-EDTA-H₂O₂ deoxyribose system but decreased OH generation in the Fe³⁺- ascorbate-H₂O₂ deoxyribose system, indicating that these compounds can both chelate iron ions and also readily donate electrons for redox cycling of Fe³⁺. The meta-dihydroxycoumarin did not show this behaviour, but was an effective scavenger of hypochlorous acid, a property shared by only one other compound. Several other coumarins with one or more hydroxyl substituents were also capable of effectively removing Superoxide anions (ic₅₀ 3.7–72 μM), although some could not be quantified due to direct rapid reduction of cytochrome c. We conclude that several compounds, notably 5,7-dihydroxy-4-methylcoumarin, possess beneficial biochemical profiles of interest in relation to pathophysiological processes dependent upon reactive oxygen species.

References (31)

RA Larson
The antioxidants of higher plants
Phytochemistry
(1988)
A Mora et al.
Structure-activity relationships of polymethoxyflavones and other flavonoids as inhibitors of non-enzymic lipid peroxidation
Biochem Pharmacol
(1990)
Y Ozaki et al.
A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function
Biochem Pharmacol
(1986)
GJ Quinlan et al.
Action of lead (II) and aluminium (III) ions on iron-stimulated lipid peroxidation in liposomes, erythrocytes and rat liver microsomal fractions
Biochim Biophys Acta
(1988)
MJ Laughton et al.
Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin
Biochem Pharmacol
(1989)
B Halliwell et al.
Formation of a thiobarbituric acid-reactive substance from deoxyribose in the presence of iron salts
FEBS Lett
(1981)
B Halliwell et al.
The deoxyribose method: a simple “test tube” assay for determination of rate constants for reactions of hydroxyl radicals
Anal Biochem
(1987)
OI Aruoma et al.
The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid
Free Rad Biol Med
(1989)
B Halliwell
Use of desferrioxamine as a ‘probe’ for iron-dependent formation of hydroxyl radicals
Biochem Pharmacol
(1985)
OI Aruoma et al.
The role of iron in ascorbate-dependent deoxyribose degradation. Evidence consistent with a site-specific hydroxyl radical generation caused by iron ions bound to the deoxyribose molecule
J Inorg Biochem
(1987)

JM McCord et al.

Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein)

J Biol Chem

(1969)

MJ Laughton et al.

Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives. Relationship to antioxidant activity and to iron ion-reducing ability

Biochem Pharmacol

(1991)

B Halliwell

Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action?

Free Rad Biol Med

(1989)

JB Porter et al.

The development of iron chelating drugs

RDM Murray et al.

The Natural Cowmarins

(1982)

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Citation Excerpt :
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^∗: On leave from Department of Pharmacology, University of Valencia, 46010 Valencia, Spain.

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Interactions of a series of coumarins with reactive oxygen species: Scavenging of superoxide, hypochlorous acid and hydroxyl radicals

Abstract

Phytochemistry

Biochem Pharmacol

Biochem Pharmacol

Biochim Biophys Acta

Biochem Pharmacol

FEBS Lett

Anal Biochem

Free Rad Biol Med

Biochem Pharmacol

J Inorg Biochem

J Biol Chem

Biochem Pharmacol

Free Rad Biol Med

The Natural Cowmarins