Inhibition of oxidation of low-density lipoprotein by a novel antioxidant, BO-653, prepared by theoretical design

Arch Biochem Biophys. 1997 Nov 1;347(1):141-7. doi: 10.1006/abbi.1997.0331.

Abstract

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran (BO-653) is a novel antioxidant synthesized by theoretical designing based on the previous experimental findings and consideration. The antioxidant activities of BO-653 against the oxidative modification of low-density lipoprotein (LDL) induced by free radicals were studied. BO-653 was consumed faster than endogenous alpha-tocopherol and inhibited the formation of lipid hydroperoxides, which was observed during the consumption of alpha-tocopherol. Doxyl stearic acids incorporated into LDL as spin probes competed with the antioxidants in scavenging radicals. It was found that the efficacy of radical scavenging by alpha-tocopherol became smaller as the radical went deeper into the interior of LDL particle, whereas that by BO-653 did not change. Ascorbic acid in the aqueous phase spared alpha-tocopherol efficiently during oxidation. On the other hand, the sparing effect of ascorbic acid for BO-653 was not remarkable, unlike that for alpha-tocopherol, which implied different locations of radicals derived from BO-653 and alpha-tocopherol within the LDL particle. It was concluded that BO-653 protected LDL from oxidative modification efficiently by scavenging peroxyl radicals and by reducing alpha-tocopheroxyl radicals and that this novel antioxidant might act as a potent inhibitor of development of atherosclerosis.

MeSH terms

  • Amidines / pharmacology
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Apolipoproteins B / metabolism
  • Arteriosclerosis / drug therapy
  • Ascorbic Acid / pharmacology
  • Azo Compounds / metabolism
  • Azo Compounds / pharmacology
  • Benzofurans / pharmacology*
  • Cyclic N-Oxides / metabolism
  • Drug Design
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacology
  • Humans
  • Kinetics
  • Lipid Peroxidation / drug effects*
  • Lipid Peroxides / antagonists & inhibitors
  • Lipoproteins, LDL / antagonists & inhibitors
  • Lipoproteins, LDL / metabolism*
  • Nitriles / metabolism
  • Nitriles / pharmacology
  • Oxidants / pharmacology
  • Oxidation-Reduction
  • Peroxides / pharmacology
  • Rabbits
  • Vitamin E / pharmacology

Substances

  • 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran
  • Amidines
  • Antioxidants
  • Apolipoproteins B
  • Azo Compounds
  • Benzofurans
  • Cyclic N-Oxides
  • Free Radical Scavengers
  • Lipid Peroxides
  • Lipoproteins, LDL
  • Nitriles
  • Oxidants
  • Peroxides
  • 2,2'-azobis(2,4-dimethylvaleronitrile)
  • Vitamin E
  • 12-doxylstearic acid
  • 2,2'-azobis(2-amidinopropane)
  • Ascorbic Acid