Effect of flavonol derivatives on the carrageenin-induced paw edema in therat and inhibition of cyclooxygenase-1 and 5-lipoxygenase in vitro

Alkoxyflavonols were synthesized by the Algar-Flynn-Oyamada (AFO) cyclizati on of chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyf lavonols by refluxing in hydroiodic acid. The alkoxyflavonols 3-hydroxy-2-( 2,3,4-trimethoxy- phenyl)-4N-chromen-4-one (6), 2-(4-ethoxyphenyl)-3-hydrox y-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 tr ihydroxy derivative 3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one ( 18) (18) displayed high anti-inflammatory activity in carrageenin-induced r at paw edema. Additionally, the inhibition of enzymes of the arachidonic ac id cascade by the derivatives was investigated in vitro. In contrast to the natural compound quercetin, the compounds were more potent inhibiting cycl ooxygenase-l than 5-lipoxygenase except for 3-hydroxy-7-methoxy-2-(4-methox yphenyl)-4N-chromen-4-one (5). No correlation between the anti-inflammatory activity in the rat paw edema test and the inhibition of 5-lipoxygenase or cyclooxygenase-1 could be observed. In conclusion, the present results sug gest that other effects than inhibition of these enzymes of the arachidonic acid cascade are important for the anti-inflammatory activity of the inves tigated alkoxyflavonols.