In Vitro Antioxidant versus Metal Ion Chelating Properties of Flavonoids: A Structure-Activity Investigation

Abstract

Natural flavonoids such as quercetin, (+)catechin and rutin as well as four methoxylated derivatives of quercetin used as models were investigated to elucidate their impact on the oxidant and antioxidant status of human red blood cells (RBCs). The impact of these compounds against metal toxicity was studied as well as their antiradical activities with DPPH assay. Antihemolytic experiments were conducted on quercetin, (+)catechin and rutin with excess of Fe, Cu and Zn (400 μM), and the oxidant (malondialdehyde, carbonyl proteins) and antioxidant (reduced glutathione, catalase activity) markers were evaluated. The results showed that Fe and Zn have the highest prooxidant effect (37 and 33% of hemolysis, respectively). Quercetin, rutin and (+)catechin exhibited strong antioxidant properties toward Fe, but this effect was decreased with respect to Zn ions. However, the Cu showed a weak antioxidant effect at the highest flavonoid concentration (200 μM), while a prooxidant effect was observed at the lowest flavonoid concentration (100 μM). These results are in agreement with the physico-chemical and antiradical data which demonstrated that binding of the metal ions (for FeNTA: (+)Catechin, KLFeNTA = 1.6(1) × 106 M-1 > Rutin, KLFeNTA = 2.0(9) × 105 M-1 > Quercetin, KLFeNTA = 1.0(7) × 105 M-1 > Q35OH, KLFeNTA = 6.3(8.7) × 104 M-1 > Quercetin3’4’OH and Quercetin 3OH, KLFeNTA ~ 2 × 104 M-1) reflects the (anti)oxidant status of the RBCs. This study reveals that flavonoids have both prooxidant and antioxidant activity depending on the nature and concentration of the flavonoids and metal ions.

Structure–Activity Relationship and Prediction of the Electron‐Transfer Potential of the Xanthones Series

“…Previously, several studies reported that the catechol moiety played a critical role in phenolic antioxidants . However, Woodman insisted on a minor role of the catechol moiety .…”

“…Moreover, all subtypes are composed of a dihedral angle between the B ring and the A/C fused rings. Thus, it is difficult to predict the ET (or antioxidant) potential of flavonoids, regardless of the amount of antioxidant structure–activity relationship studies …”

“…For example, among the thousands of documented flavonoids, there are only a few flavonoids with a hydroquinone moiety, and they include rhodionin, 5,8‐dihydroxy‐3,6,7‐trimethoxyflavone, 5,8‐dihydroxy‐6,7‐dimethoxyflavone, 5,8‐dihydroxy‐6,7,4′‐trimethoxyflavone, 5,8‐dihydroxy‐6,7,3′,4′,5′‐pentamethoxyflavone, and isothymusin . This hydroquinone moiety is hardly found in other phenolics . As a result, its antioxidant role has not yet been explored.…”

Comparative Study of 1,1‐Diphenyl‐2‐picryl‐hydrazyl Radical (DPPH•) Scavenging Capacity of the Antioxidant Xanthones Family

“…These pathways can also be found in the DPPH•‐scavenging reaction . In fact, the DPPH•‐scavenging assay has been successfully used to systematically evaluate the antioxidant capacities of flavonoids and anthocyanidins ,,…”

Flavonoid Complexes as Promising Anticancer Metallodrugs

“…Prooxidant activity is thought to be directly proportional to the total number of hydroxyl groups [25], especially in the B-ring [26], and the concentration of the flavonoid [27].…”