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Discovery of relaxant flavonols without antioxidant activity
Author(s) -
Qin Cheng Xue,
Williams Spencer J,
Hughes Richard A,
Woodman Owen L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.912.2
Subject(s) - flavonols , chemistry , antioxidant , xanthine oxidase , cardioprotection , xanthine , superoxide , quercetin , biochemistry , pharmacology , ischemia , medicine , enzyme
3′,4′‐dihydroxyflavonol (DiOHF) is an antioxidant and vasorelaxant that reduces injury after ischaemia and reperfusion. We synthesized a series of compounds based on DiOHF with pharmacophore modifications at the 3′ and 4′ positions on the B ring and examined the biological activity for the 18 novel flavonols [4′‐substituted flavonols (H; OH; OMe; Me; Cl; CF 3 ; C(CH 3 ) 3 ); 3′‐substituted flavonols (H; OH; OMe; Me; Cl; CF 3 ) and 4′‐hydroxy‐3′‐substituted flavonols (H; OH; OMe; Me; Br; CF 3 ; C(CH 3 ) 3 )]. Each flavonol was examined for its ability to relax rat isolated aortic rings precontracted with KCl (30 mM). The most active flavonols (Rmax>80%) were those with a hydroxy group at the 4′ position (eg, DiOHF, pEC 50 =5.30±0.07, Rmax=102±1%; 4′‐OH‐3′‐OCH 3 flavonol, 5.35±0.03, 98±2%; 4′‐OCH 3 flavonol, Rmax=37±4%). The antioxidant activity of each flavonol was then assessed by lucigenin‐enhanced chemiluminescence and assays to assess endothelial dysfunction due to oxidant stress. With the exception of DiOHF, none of these flavonols (at 10 ‐5 M) were able to significantly scavenge superoxide radical or prevent pyrogallol or xanthine/xanthine oxidase‐induced endothelial dysfunction. The discovery of vasorelaxant flavonols without antioxidant activity, such as 4′‐OH‐3′‐OCH 3 flavonol, will assist in investigating the mechanism of flavonol‐induced cardioprotection.