Triterpene Biosynthesis in the Latex of Euphorbia lathyris: Effect of Calmodulin Antagonists and Chlorinated Phenoxy Compounds

AUTOR(ES)
RESUMO

Recognized calmodulin antagonists and chlorinated phenoxyalkylamines were tested as inhibitors of mevalonate incorporation into triterpenols and their fatty acid esters in a centrifuged pellet from the latex of Euphorbia lathyris. The calmodulin antagonists, chlorpromazine (II), fluphenzine, and trifluoperazine were good inhibitors; I50 values for II and trifluoperazine were 150 and 55 micromolar, respectively. Inhibition by the phenoxyalkylamines increased with increasing chlorine substitution, and I50 for 2-(pentachlorophenoxy)ethyl N,N-diethylamine (IX) was 35 micromolar. The calmodulin-stimulated phosphodiesterase catalyzed hydrolysis of cAMP was used as an assay to quantitate the calmodulin antagonism of the tested compounds. Compounds II and IX were calmodulin antagonists over a concentration range similar to their effective range in the biosynthesis of triterpenes. The antagonism of the chlorinated phenoxy compounds increased in parallel to their inhibitory effect upon triterpene biosynthesis.

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