Antioxidant properties of N-(4-hydroxyphenyl)retinamide (fenretinide)

Biol Pharm Bull. 2000 Feb;23(2):222-5. doi: 10.1248/bpb.23.222.


Fenretinide, N-(4-hydroxyphenyl)retinamide (4-HPR), is a cancer chemopreventive and antiproliferative agent whose mechanism of action is unknown. 4-HPR is a potent inducer of apoptosis in HL60 human leukemia cells which generates intracellular reactive oxygen species. The structural similarity of retinoic acid (RA), 4-HPR, and alpha-tocopherol (vitamin E) led us to investigate whether 4-HPR exhibits antioxidant activity. It was found that 4-HPR scavenged alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals in a 1:1 ratio in contrast to vitamin E, where a 1:2 ratio relative to DPPH radicals was observed. In addition, linoleic acid peroxidation initiated by hydroxyl radicals was decreased by 4-HPR to the same extent as by vitamin E. Furthermore, lipid peroxidation in rat liver microsomes was reduced by 4-HPR to a greater extent than by vitamin E. Based on these results, 4-HPR appears to be an effective antioxidant that may have clinical utility for diseases treated with vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Ascorbic Acid / chemistry
  • Bepridil / analogs & derivatives
  • Bepridil / chemistry
  • Bepridil / metabolism
  • Biphenyl Compounds
  • Fenretinide / pharmacology*
  • Free Radical Scavengers / pharmacology
  • Free Radicals / chemistry
  • Free Radicals / metabolism
  • Humans
  • Hydroxyl Radical
  • In Vitro Techniques
  • Linoleic Acid / chemistry
  • Lipid Peroxidation / drug effects
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Picrates*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Retinoids / metabolism
  • Vitamin E / chemistry


  • Antineoplastic Agents
  • Antioxidants
  • Biphenyl Compounds
  • Free Radical Scavengers
  • Free Radicals
  • Picrates
  • Reactive Oxygen Species
  • Retinoids
  • Vitamin E
  • Fenretinide
  • Hydroxyl Radical
  • Bepridil
  • Linoleic Acid
  • 1,1-diphenyl-2-picrylhydrazyl
  • Ascorbic Acid