Effects of anthrapyrazole antineoplastic agents on lipid peroxidation

Biochem Biophys Res Commun. 1986 Nov 14;140(3):797-807. doi: 10.1016/0006-291x(86)90704-7.

Abstract

The effects of three anthrapyrazoles and an aminoacridine derivative on doxorubicin- and iron-stimulated lipid peroxidation in rabbit hepatic microsomes have been characterized. Two anthrapyrazoles, CI-937 and CI-942, were potent inhibitors of lipid peroxidation with 15 microM drug inhibiting the rate of peroxidation 70 to 90%. In contrast CI-941 was relatively ineffective in inhibiting lipid peroxidation with only 35% inhibition occurring at 100 microM drug. CI-921, an aminoacridine derivative, diminished lipid peroxidation by 65% at 15 microM. All four drugs failed to decrease the rate of doxorubicin-stimulated NADPH oxidation at concentrations less than 50 microM, suggesting that inhibition of lipid peroxidation was not the result of diminished enzyme activity. CI-937 formed a 2:1 complex with ferric ion, KD = 47 microM, which was reversible with EDTA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amsacrine / analogs & derivatives
  • Amsacrine / pharmacology
  • Animals
  • Anthraquinones / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Doxorubicin / pharmacology
  • In Vitro Techniques
  • Iron / pharmacology
  • Lipid Peroxides / biosynthesis*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Pyrazoles / pharmacology*
  • Pyrazolones*
  • Rabbits

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • Lipid Peroxides
  • Pyrazoles
  • Pyrazolones
  • Amsacrine
  • losoxantrone
  • Doxorubicin
  • teloxantrone
  • Iron
  • asulacrine
  • piroxantrone