Protection of Flavonoids Against Lipid Peroxidation: The Structure Activity Relationship Revisited (original) (raw)

The inhibition of the lipid peroxidation, induced by iron and ascorbate in rat liver microsomes, by phenols and flavones was studied. The activity of phenol was enhanced by electron donating substituents, denoted by the Hammett sigma (s ). The concentration of the substituted phenols giving 50% inhibition (IC 50 ) of lipid peroxidation gave a good correlation with the s of the substituent ðlnð1=IC 50 Þ ¼ 28:92s þ 5:80 ðR ¼ 0:94; p , 0:05ÞÞ: In flavones two pharmacophores for the protection against lipid peroxidation were pinpointed: (i) a catechol moiety as ring B and (ii) an OH-group at the 3 position with electron donating groups at the 5 and/or 7 position in the AC-ring. An example of a flavone with the latter pharmacophore is galangin (3,5,7-trihydroxyflavone) where the reactivity of the 3-OH-group is enhanced by the electron donating effect of the 5-and 7-OH-groups. This is comparable to the effect of electron donating substituents on the activity of phenol.