Inhibition of xanthine oxidase by phenolic conjugates of methylated quinic acid.
The caffeoyl conjugates of prenylhydroquinone glucoside and of quinic acid, either in the carboxyl-free or carboxymethyl forms, isolated from Phagnalon rupestre (Asteraceae), showed inhibitory activity on lipid peroxidation induced by Fe 2+/ascorbate and by CCl4/NADPH in rat liver microsomes, with IC50 values ranging from 3 to 11 microM. After having demonstrated their effect on the xanthine oxidase-regulated superoxide production, the active compounds were tested for the direct inhibition of this enzyme. Methylated dicaffeoylquinic conjugates competitively inhibited the enzyme and the highest potency was obtained for the 4,5-diester, with an IC50 value of 3.6 microM, nearly ten times lower than that of the 3,5-analogue. In conclusion, the presence of the caffeoyl moiety is essential for both the antiperoxidative and radical scavenging activities, and the methylation of the quinic carboxyl group enhances the potency on xanthine oxidase inhibitory activity.
Góngora
Luis
L
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Burjassot, Spain.
Máñez
Salvador
S
Giner
Rosa María
RM
Recio
María del Carmen
Mdel C
Schinella
Guillermo
G
Ríos
José Luis
JL
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019659:Asteraceae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006873:Hydroquinones / Q000737:chemistry; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D010636:Phenols; D010936:Plant Extracts; C472707:caffeoylquinic acid; D011801:Quinic Acid; D014969:Xanthine Oxidase; C031927:hydroquinone