Effects of anthrapyrazole antineoplastic agents on lipid peroxidation.
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.
D000677:Amsacrine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D047069:Pyrazolones; D011817:Rabbits
D000880:Anthraquinones; D000970:Antineoplastic Agents; D008054:Lipid Peroxides; D011720:Pyrazoles; D047069:Pyrazolones; D000677:Amsacrine; C050637:losoxantrone; D004317:Doxorubicin; C046658:teloxantrone; D007501:Iron; C042315:asulacrine; C046659:piroxantrone