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

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-trimethoxyphenyl)-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 compounds 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 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 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.