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• W2056580245 abstract "Sixteen synthetic or plant-derived coumarins of dietary importance with different patterns of substitution were tested for their capacity to scavenge superoxide and for their cytotoxicity. Superoxide was generated by human polymorphonuclear leukocytes stimulated by phorbol myristate acetate and was measured using the reduction of ferricytochrome c or of nitrobule tetrazolium (NBT). Eleven of the coumarins, all lacking dihydroxy substitution, did not scavenge superoxide. Of the remaining five, the most potent scavenger was fraxetin (7,8-dihydroxy-6-methoxycoumarin) with an IC50 (concentration producing 50% inhibition) of 2.3 microM in the cytochrome assay and 5.8 microM using NBT. The other four coumarins (all containing ortho-dihydroxy catechol functions, and found previously to be pro-oxidant in cell-free systems by virtue of reduction of ferric to ferrous ions), themselves rapidly reduced cytochrome c. Therefore their effects on superoxide were measured using NBT, yielding IC50 values in the range 8.5 to 82.0 microM. Fraxetin and the other active and inactive coumarins were not directly cytotoxic at 100 microM to leukocytes or to erythrocytes, as shown by their failure to cause release of cytosolic lactate dehydrogenase or to cause haemolysis, respectively. However, all five dihydroxylated pro-oxidant coumarins were toxic to NS20Y neuroblastoma cells in 24 hr culture, whereas the other eleven coumarins were nontoxic. We conclude that 7,8-dihydroxylated coumarins such as fraxetin are agents which are not themselves directly cytotoxic and are capable of direct scavenging of superoxide anion radicals, an action which might be protective at sites of leukocyte activation during inflammation. However, in the presence of free ferric ions they may exert potentially damaging pro-oxidant actions, including cytotoxicity. This series of compounds provides a useful basis for structure-activity studies designed to achieve separation or combination of these properties." @default.
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• W2056580245 date "1994-08-01" @default.
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• W2056580245 title "Superoxide scavenging activity in leukocytes and absence of cellular toxicity of a series of coumarins" @default.
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• W2056580245 doi "https://doi.org/10.1016/0006-2952(94)90273-9" @default.
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