Dietary Flavonoids as Xanthine Oxidase Inhibitors: Structure-Affinity and Structure-Activity Relationships.
The flavonoid family has been reported to possess a high potential for inhibition of xanthine oxidase (XO). This study concerned the structural aspects of inhibitory activities and binding affinities of flavonoids as XO inhibitors. The result indicated that the hydrophobic interaction was important in the binding of flavonoids to XO, and the XO inhibitory ability increased generally with increasing affinities within the class of flavones and flavonols. The planar structure and the C2═C3 double bonds of flavonoids were advantageous for binding to XO and for XO inhibition. Both the hydroxylation on ring B and the substitution at C3 were unfavorable for XO inhibition more profoundly than their XO affinity. The methylation greatly reduced the inhibition (0.75-3.07 times) but hardly affected the affinity. The bulky sugar substitutions of flavonoids decreased the inhibition (1.69-1.99 times) and lowered the affinities (4.20-9.22 times) to different degrees depending on the conjunction site.
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Suyun
S
Lin
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Guowen
G
Zhang
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Yijing
Y
Liao
State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China.
Junhui
J
Pan
School of Biological Sciences, The University of Auckland , Auckland 1142, New Zealand.
Deming
D
Gong
D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism; D006900:Hydroxylation; D007700:Kinetics; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000737:chemistry* / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D014969:Xanthine Oxidase
flavonoids; inhibition; molecular modeling; structure−activity relationship; xanthine oxidase