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Effect of Flavonol Derivatives on the Carrageenin‐Induced Paw Edema in the Rat and Inhibition of Cyclooxygenase‐1 and 5‐Lipoxygenase in Vitro
Author(s) -
Sobottka Andrea M.,
Werner Wolfgang,
Blaschke Gottfried,
Kiefer Werner,
Nowe Ulrike,
Dannhardt Gerd,
Schapoval Elfrides E. S.,
Schenkel Eloir P.,
Scriba Gerhard K.E.
Publication year - 2000
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/1521-4184(20007)333:7<205::aid-ardp205>3.0.co;2-y
Subject(s) - cyclooxygenase , chemistry , arachidonic acid , in vitro , lipoxygenase , edema , carrageenan , anti inflammatory , enzyme , arachidonate 5 lipoxygenase , pharmacology , quercetin , biochemistry , stereochemistry , antioxidant , medicine , psychiatry
Alkoxyflavonols were synthesized by the Algar‐Flynn‐Oyamada (AFO) cyclization of chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyflavonols by refluxing in hydroiodic acid. The alkoxyflavonols 3‐hydroxy‐2‐(2,3,4‐trimethoxy‐phenyl)‐ 4H ‐chromen‐4‐one ( 6 ), 2‐(4‐ethoxyphenyl)‐3‐hydroxy‐ 4H ‐ chromen‐4‐one ( 7 ), 2‐(4‐butoxyphenyl)‐3‐hydroxy‐ 4H ‐ chromen‐4‐one ( 10 ), and 2‐(3‐n‐butoxyphenyl)‐3‐hydroxy‐ 4H ‐ chromen‐4‐one ( 11 ) as well as the trihydroxy derivative 3‐hydroxy‐ 2‐(3,4,5‐trihydroxyphenyl)‐ 4H ‐chromen‐4‐one ( 18 ) displayed high anti‐inflammatory activity in carrageenin‐induced rat paw edema. Additionally, the inhibition of enzymes of the arachidonic acid cascade by the derivatives was investigated in vitro. In contrast to the natural compound quercetin, the com‐pounds were more potent inhibiting cyclooxygenase‐1 than 5‐lipoxygenase except for 3‐hydroxy‐7‐methoxy‐2‐(4‐methoxyphenyl)‐ 4H ‐chromen‐4‐one ( 5 ). No correlation between the antiinflammatory activity in the rat paw edema test and the inhibition of 5‐lipoxygenase or cyclooxygenase‐1 could be observed. In conclusion, the present results suggest that other effects than inhibition of these enzymes of the arachidonic acid cascade are important for the anti‐inflammatory activity of the investigated alkoxyflavonols.