Antioxidant properties of di-tert-butylhydroxylated flavonoids

Epidemiological evidence suggests an inverse relationship between dietary intake of flavonoids and cardiovascular risk. The biological activities of flavonoids are related to their antioxidative effects, but they also can be mutagenic, due to the prooxidant activity of the catechol pattern. To prevent these problems, we synthesized new flavonoids where one or two di-tert-butylhydroxyphenyl (DBHP) groups replaced catechol moiety at position 2 of the benzopyrane heterocycle. Two DBHP moieties can also be arranged in an arylidene structure or one DBHP fixed on a chalcone structure. Position 7 on the flavone and arylidene or position 4 on the chalcone was substituted by H, OCH3, or OH. New structures were compared with quercetin and BHT in an LDL oxidation system induced by Cu(II) ions. Arylidenes and chalcones had the best activities (ED50 = 0.86 and 0.21) compared with vitamin E, BHT, and quercetin (ED50 = 10.0, 7.4, and 2.3 muM). Activity towards stable free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) was measured by log Z and ECR50 parameters. Synthesized flavones proved to be poor DPPH radical scavengers, the activity increasing with the number of DBHP units. In contrast, arylidenes and chalcones were stronger DPPH radical scavengers (log Z > 3, 0.3 < ECR50 < 2.12) than BHT (log Z = 0.75, ECR50 = 12.56) or quercetin (log Z = 2.76, ECR50 = 0.43). Unlike quercetin, synthesized compounds neither chelated nor reduced copper, proving that these new flavonoids had no prooxidant activity in vitro. (C) 2000 Elsevier Science Inc.