The Relation of Structure to Antioxidant Activity of Quercetin and Some of Its Derivatives I. Primary Activity

Abstract

SUMMARY The primary antioxidant activity of quercetin and some of its derivatives was studied in the 36–70°C range in dry systems, using two fatty‐ester substrates, respectively with linoleate and linolenate, as the main constituent undergoing oxidation. Metal contamination was avoided as far as possible, and any residual traces of metals in the thoroughly purified esters were chelated with citric acid. Methylation of the 3, or 5, or 3 and 7, or 5 and 7 hydroxyls of the quercetin molecule led to considerable reduction of the antioxidant activity, while reduction due to methylation of the 7 hydroxyl was slight. Methylation of the 3′, or 4′, or 3′ and 4′ hydroxyls, or of any single hydroxyl of the B ring, and of an additional hydroxyl or hydroxyls of the A ring, led to a drastic reduction (to 11% or less); the 3,7,3′,4′ tetramethoxy derivative was found to be completely inactive. Hydrogenation of the 2,3 double bond resulted in an antioxidant (dihydroquercetin) with only about half the activity of qnercetin. The primary antioxidant activity of quercetin seems to be a function of the molecule as a whole and cannot be regarded as an additive property of active hydroxyls. The effect produced by methylation of a particular hydroxyl may, however, be related to the probability of formation of a stabilized free radical by the hydroxyl in question. The type of the substituted alkyl radical had little or no effect on the activity of the derivative, but replacement of a hydroxyl with hydrogen failed to produce the same effect as methylation of the same hydroxyl. No indication was found of pro‐oxidant activity of the meta‐hydroxyl grouping in the A ring.

Cooperation of Quercetin With Ascorbate in the Protection of Photosensitized Lysis of Human Erythrocytes in the Presence of Hematoporphyrin

“…This may be due to saturation of the protection of hemolysis by quercetin at around 100 pM (Sorata , 1984). Quercetin did not function as a prooxidant as reported previously (Letan, 1966). Figure 2 shows the effect of ascorbate on quercetin oxidation in erythrocyte suspensions.…”

Comparison of the Protective Effect of Various Flavonoids Against Lipid Peroxidation of Erythrocyte Membranes (Induced by Cumene Hydroperoxide)

“…However, in our membrane system, flavone (which exhibited high hydrophobic properties) could be in part solubilized in the lipid phase of the RBCmb; but even so, we did not observe any protective effect with increasing flavone concentration. To obtain a significant antioxidant effect, the presence of an OH group on both aromatic rings (A and B) seems to be necessary, as already shown in previous reports (Letan, 1966;Baumann et al, 1979). We can also emphasize that the substitution of an OH group markedly reduced antioxidant effect (Table I).…”

Natural Antioxidants

“…Many flavones occur as glycosides, but it is the aglycone that provides the antioxidant activity of the molecule. Crawford, et al (1961) established the essentiality of the 3', 4' hydroxyls in quercetin and Letan (1966a) suggested that the 4' hydroxyl was capable of forming stabilized free radicals more easily. Letan (1966b) also suggested that copper complexing of quercetin relates to the 4-keto group coupling through either the 3 or the 5 hydroxyl.…”