Effect of Flavonol Derivatives on the Carrageenin-Induced Paw Edema in the Rat and Inhibition of Cyclooxygenase-1 and 5-Lipoxygenase in Vitro

Abstract

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.