Interactions between calvatic acid and related compounds with rat liver microsomes

In this study we examined the interactions of liver microsomes with the antibiotic calvatic acid and with structural analogues, some of which had shown antimicrotubular properties. These drugs decreased cytochrome P-450 content differently according to the substitutions on the azoxy function and the ethoxycarbonyl derivatives were found to be the most effective ones. The decrease in cytochrome P-450 could be prevented by addition of cysteine or GSH, suggesting an involvement of sulphydryl groups. Furthermore, chromatographic analyses showed that ethoxycarbonyl derivatives were completely metabolized, and this would explain the different behaviour of these compounds towards microtubular protein when they were incubated with purified bovine brain protein or with liver or hepatoma extracts.