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Antioxidant effects of coumarins include direct radical scavenging, metal chelation and inhibition of ROS-producing enzymes
T. Filipský, M. Říha, K. Macáková, E. Anzenbacherová, J. Karlíčková, P. Mladěnka,
Language English Country Netherlands
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
- MeSH
- Chelating Agents chemistry metabolism pharmacology MeSH
- Cyclooxygenase 2 metabolism MeSH
- Enzyme Inhibitors chemistry metabolism pharmacology MeSH
- Coumarins chemistry metabolism pharmacology MeSH
- Humans MeSH
- Lipoxygenase metabolism MeSH
- Copper chemistry metabolism MeSH
- Oxidative Stress drug effects MeSH
- Peroxidase antagonists & inhibitors metabolism MeSH
- Reactive Oxygen Species antagonists & inhibitors metabolism MeSH
- Free Radical Scavengers chemistry metabolism pharmacology MeSH
- Nitric Oxide Synthase Type II antagonists & inhibitors metabolism MeSH
- Structure-Activity Relationship MeSH
- Xanthine Oxidase antagonists & inhibitors metabolism MeSH
- Iron chemistry metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Coumarins represent a large group of 1,2-benzopyrone derivatives which have been identified in many natural sources and synthetized as well. Several studies have shown that their antioxidant capacity is not based only on direct scavenging of reactive oxygen and nitrogen species (RONS) but other mechanisms are also involved. These include: a) the chelation of transient metals iron and copper, which are known to catalyse the Fenton reaction; and b) the inhibition of RONS-producing enzymes (e.g. xanthine oxidase, myeloperoxidase and lipoxygenase), suggesting that mechanism(s) involved on cellular level are complex and synergistic. Moreover, many factors must be taken into account when analysing structure-antioxidant capacity relationships of coumarins due to different in vitro/in vivo methodological approaches. The structural features necessary for the direct RONS scavenging and metal chelation are apparently similar and the ideal structures are 6,7-dihydroxy- or 7,8-dihydroxycoumarins. However, the clinical outcome is unknown, because these coumarins are able to reduce copper and iron, and may thus paradoxically potentiate the Fenton chemistry. The similar structural features appear to be associated with inhibition of lipoxygenase, probably due to interference with iron in its active site. Contrarily, 6,7-dihydroxycoumarin seems to be the most active coumarin in the inhibition of xanthine oxidase while its derivative bearing the 4-methyl group or 7,8-dihydroxycoumarin are less active or inactive. In addition, coumarins may hinder the induction of inducible NO-synthase and cyclooxygenase- 2. Sparse data on inhibition of myeloperoxidase do not enable any clear conclusion, but some coumarins may block it.
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- $a Coumarins represent a large group of 1,2-benzopyrone derivatives which have been identified in many natural sources and synthetized as well. Several studies have shown that their antioxidant capacity is not based only on direct scavenging of reactive oxygen and nitrogen species (RONS) but other mechanisms are also involved. These include: a) the chelation of transient metals iron and copper, which are known to catalyse the Fenton reaction; and b) the inhibition of RONS-producing enzymes (e.g. xanthine oxidase, myeloperoxidase and lipoxygenase), suggesting that mechanism(s) involved on cellular level are complex and synergistic. Moreover, many factors must be taken into account when analysing structure-antioxidant capacity relationships of coumarins due to different in vitro/in vivo methodological approaches. The structural features necessary for the direct RONS scavenging and metal chelation are apparently similar and the ideal structures are 6,7-dihydroxy- or 7,8-dihydroxycoumarins. However, the clinical outcome is unknown, because these coumarins are able to reduce copper and iron, and may thus paradoxically potentiate the Fenton chemistry. The similar structural features appear to be associated with inhibition of lipoxygenase, probably due to interference with iron in its active site. Contrarily, 6,7-dihydroxycoumarin seems to be the most active coumarin in the inhibition of xanthine oxidase while its derivative bearing the 4-methyl group or 7,8-dihydroxycoumarin are less active or inactive. In addition, coumarins may hinder the induction of inducible NO-synthase and cyclooxygenase- 2. Sparse data on inhibition of myeloperoxidase do not enable any clear conclusion, but some coumarins may block it.
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- $a Mladěnka, Přemysl $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Krelove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. mladenkap@faf.cuni.cz.
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