Anti- and pro-oxidant activity of rutin and quercetin derivatives.
Some semi-synthetic flavonoids, particularly derivatives of rutin, are used as therapeutic agents in the treatment of diseases involving free radicals. Here, for the first time, a complete study has been made of the relationship between the structure of such molecules and their superoxide, hydroxyl and peroxyl radical scavenging activity. The molecules chosen for this study were rutin, its aglycone (quercetin), and their methyl ethyl and hydroxyl-ethyl derivatives. Our results are consistent with the general agreement on the structural requirements for free radical scavenging activity. Moreover, we have shown that alkylation of the hydroxyl in position 7 enhanced the scavenging, and also that in a Fenton reaction system, some quercetin derivatives with free catechol moiety or free hydroxyl in position 3 (or both) were pro-oxidant, through superoxide radical and hydrogen peroxide production. Although the structural features needed for pro-oxidant activity are not entirely clear, it appears that to avoid pro-oxidant behaviour, the hydroxyl group in position 3 should be blocked to prevent its auto-oxidation. Thus, flavonoids cannot only be considered purely as antioxidants, since under certain reaction conditions they can also display pro-oxidant activity. This unexpected behaviour could explain, in part, the observed toxicity of some flavonoids in-vivo.
Kessler
Marc
M
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie de Strasbourg, 74 route du Rhin, BP 24, F-67401 Illkirch, France.
Ubeaud
Geneviève
G
Jung
Louis
L
D000975:Antioxidants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010545:Peroxides / Q000737:chemistry; D011794:Quercetin / Q000494:pharmacology*; D012431:Rutin / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D010545:Peroxides; C049375:perhydroxyl radical; D017665:Hydroxyl Radical; D012431:Rutin; D011794:Quercetin