Abstract
The antibiotic cycloheximide inhibits protein synthesis in animal cells. The effect of a number of derivatives, related compounds and stereoisomers of cycloheximide on protein synthesis in animal cells and in extracts prepared from animal cells, was studied. Substitution of the oxygen attached to carbon-1 of the cyclohexanone ring or esterification of the hydroxyl group attached to the α-carbon of the hydroxyethyl-glutarimide side chain greatly diminishes inhibitory activity. The absolute configuration of the cyclohexanone ring is important for activity, but a cyclic ketone is not necessary. Compounds with a substitution by an acetoxy or hydroxyl group of the hydrogen attached to carbon-4 of the cyclohexanone ring, as in acetoxycycloheximide and streptovitacin A, respectively, inhibit protein synthesis better than cycloheximide. The results obtained in the present investigation using animal cells are in general agreement with previous studies using yeast cells.
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