Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage

An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a–e and 4a–j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid peroxidation inhibition, PC12 cells protection from oxidative damage, and xanthine oxidase inhibition. These dihydroflavonols displayed positive quenching abilities towards O2- and DPPH free radicals, in which the majority exhibited superior antioxidant properties to Vitamin C. cis-Configurated compound (±)-3e demonstrated remarkable inhibition to LPO with an IC50 value of 1.9 ± 0.3 μM, which was apparently stronger than that of quercetin (IC50 = 6.0 ± 0.4 μM). trans-Configurated dihydroflavonol (±)-4h exhibited significant protective effect on PC12 cells against oxidative damage with an EC50 value of 41.5 ± 5.3 μM, more effective compared to that of quercetin (EC50 = 81.8 ± 8.7 μM). The 6-OH-5,7-dimethoxy analogue (±)-3d showed significant inhibition of xanthine oxidase with an IC50 value of 16.0 ± 0.8 μM, which is superior to that of allopurinol (IC50 = 23.5 ± 2.0 μM). In addition to the hypothesized action mechanism of the bio-active compounds, 3D modeling was used to analyze the relationship between the minimized-energy structures and antioxidant activities.

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