Title:Antioxidant Effects of Coumarins Include Direct Radical Scavenging, Metal Chelation and Inhibition of ROS-Producing Enzymes
Volume: 15
Issue: 5
Author(s): Tomas Filipsky, Michal Riha, Katerina Macakova, Eva Anzenbacherova, Jana Karlickova and Premysl Mladenka
Affiliation:
Keywords:
Antioxidant, Copper, Coumarins, Iron, Lipoxygenase, Myeloperoxidase, Xanthine oxidase.
Abstract: 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.