Abstract
The effects of three anthrapyrazoles and an aminoacridine derivative on doxorubincin- 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 μM 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 μM drug. CI-921, an aminoacridine derivative, diminished lipid peroxidation by 65% at 15 μM. All four drugs failed to decrease the rate of doxorubicin-stimulated NADPH oxidation at concentrations <50 μM, suggesting that inhibition of lipid peroxidation was not the result of diminished enzyme activity. CI-937 formed a 2:1 complex with ferric ion, K D = 47 μM, which was reversible with EDTA.
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