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

3-Hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one

“…For intermolecular interactions, see: Aakerö y et al (1992); Novoa et al (2006). For the synthesis, see: Bader et al (2003); Sobottka et al (2000).…”

“…= 557-558 K; lit. 555-558 K (Sobottka et al, 2000)). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.28 e Å −3 Δρ min = −0.31 e Å −3 Extinction correction: SHELXL97 (Sheldrick, 2008), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4 Extinction coefficient: 0.011 (3 Refinement.…”

3-Hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one

“…For intermolecular interactions, see: Aakerö y et al (1992); Takahashi et al (2001). For the synthesis, see: Sobottka et al (2000).…”

“…The title compound was synthesized as a result of the oxidative heterocyclization of 1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one, synthesized first by the condensation of 1-(2-hydroxyphenyl)ethanone with 4-methoxy- (Sobottka et al, 2000). The filtered product was purified chromatographically (Silica Gel, chloroform/ethanol, 20/1 v/v) and colorless crystals suitable for Xray investigations were grown from chloroform (m.p.…”

Synthesis of the flavonoid 3′,4′,5′-trimethoxyflavonol and its determination in plasma and tissues of mice by HPLC with fluorescence detection

“…TMFol was synthesized using a procedure adapted from Sobottka et al [7]: sodium (13.52 g, 0.59 mol) was dissolved in ethanol (500 ml) and 2-hydroxyacetophenone (20 g, 0.15 mol) was added. To this suspension 3,4,5-trimethoxybenzaldehyde (28.8 g, 0.15 mol) was added.…”