Antioxidant properties of N-(4-hydroxyphenyl)retinamide (fenretinide).
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.
Takahashi
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Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000737:chemistry; D015764:Bepridil / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D001713:Biphenyl Compounds; D017313:Fenretinide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010851:Picrates; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D014810:Vitamin E / Q000737:chemistry
D000970:Antineoplastic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D010851:Picrates; D017382:Reactive Oxygen Species; D012176:Retinoids; D014810:Vitamin E; D017313:Fenretinide; D017665:Hydroxyl Radical; D015764:Bepridil; D019787:Linoleic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D001205:Ascorbic Acid