title: Antioxidant effects of coumarins include direct radical scavenging, metal chelation and inhibition of ROS-producing enzymes.
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.
authors: Tomáš
authors: T
authors: Filipský
authors: Michal
authors: M
authors: Říha
authors: Kateřina
authors: K
authors: Macáková
authors: Eva
authors: E
authors: Anzenbacherová
authors: Jana
authors: J
authors: Karlíčková
authors: 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.
authors: Přemysl
authors: P
authors: Mladěnka
mesh_terms: D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D003374:Coumarins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D003300:Copper; D007501:Iron; D009195:Peroxidase; D008084:Lipoxygenase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D014969:Xanthine Oxidase