Inhibition of mitochondrial and bacterial protein synthesis by chloramphenicol

The structural requirements for the inhibition of protein synthesis in mitochondria and in bacterial extracts by chloramphenicol isomers and analogues are similar. D-threo-Chloramphenicol and its p-methylthio, p-methylsulfonyl, and p-sulfamoyl analogues equally inhibit protein synthesis in isolated rat-liver mitochondria and extracts of Escherichia coli B. Fifty percent inhibition is at 15 μM and 10 μM, respectively. Analogues with larger p-substituents on the phenyl ring or with an m-chloro group are less inhibitory in both systems. L-threo-Chloramphenicol and deacylated chloramphenicol do not inhibit mitochondrial protein synthesis; with a dichloroacetyl group replacing the acetyl group on chloramphenicol 50% inhibition is at 65 μM, and L-erythro-chloramphenicol is 2% as inhibitory as D-threo-chloramphenicol. The inhibition of protein synthesis in intact E. coli B is in the order: chloramphenicol > p-methylthio > p-methylsulfonyl > p-sulfamoyl, 50% inhibition being at 4 μM for chloramphenicol.