Structural aspects of antioxidant activity of flavonoids

Free Radic Biol Med. 1996;20(3):331-42. doi: 10.1016/0891-5849(95)02047-0.


Flavonoids, a group of naturally occurring antioxidants and iron chelators, might be used as cardioprotective agents in doxorubicin-induced cardiotoxicity, which is believed to be caused by the formation of oxygen free radicals. To investigate the underlying molecular mechanism, we tested a large group of flavonoids from all major structural subclasses on their ability to inhibit doxorubicin (enzymatically)-induced and Fe2+/ascorbate (nonenzymatically)-induced microsomal lipid peroxidation (LPO) and to chelate Fe2+. In addition, we measured half peak oxidation potentials (Ep/2). LPO inhibition data gave a good qualitative correlation with the oxidation potentials. Most flavonoids tested chelated Fe2+, but there were large differences in the chelating capacity. For good scavenging activity, a catechol moiety on ring B is required. The 3-OH moiety can function as a chelation site and can also be oxidized. The 3-OH group in combination with a C2 C3 double bond, increases the scavenging activity. Fe2+ chelation only plays a role in the LPO inhibition by less active scavengers. Chelation can then raise the activity to the level of the most active scavengers, possibly by site-specific scavenging. It can be concluded that Ep/2 values and iron chelating activity can almost completely describe the LPO inhibiting behaviour of the flavonoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology*
  • Ascorbic Acid
  • Ferrous Compounds
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology*
  • Free Radicals
  • Iron / metabolism
  • Iron Chelating Agents / pharmacology
  • Lipid Peroxidation*
  • Mice
  • Mice, Inbred BALB C
  • Microsomes / drug effects
  • Microsomes / metabolism*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Molecular Structure
  • Myocardium / metabolism
  • Regression Analysis
  • Structure-Activity Relationship


  • Antioxidants
  • Ferrous Compounds
  • Flavonoids
  • Free Radicals
  • Iron Chelating Agents
  • iron(II)-ascorbic acid complex
  • Iron
  • Ascorbic Acid