INTERACTIONS BETWEEN CALVATIC ACID AND RELATED-COMPOUNDS WITH RAT-LIVER MICROSOMES

In this study we examined the interactions of liver microsomes with th e antibiotic calvatic acid and with structural analogues, some of whic h had shown antimicrotubular properties. These drugs decreased cytochr ome P-450 content differently according to the substitutions on the az oxy function and the ethoxycarbonyl derivatives were found to be the m ost effective ones. The decrease in cytochrome P-450 could be prevente d by addition of cysteine or GSH, suggesting an involvement of sulphyd ryl groups. Furthermore, chromatographic analyses showed that ethoxyca rbonyl derivatives were completely metabolized, and this would explain the different behaviour of these compounds towards microtubular prote in when they were incubated with purified bovine brain protein or with liver or hepatoma extracts.