Analogy between in vivo and in vitro biological effect of chloramphenicol and its acetylated derivatives

Binding of Chloramphenicol and its Acetylated Derivatives to <i>Escherichia coli</i> Ribosomal Subunits

“…This is in agreement with the in vivo data obtained for this compound by the MIC determinations [5].…”

“…In the presence of 1,3-diacctoxychloramphenicol or of the 1-monoacetoxyderivative, no inhibition is observed: the amount of labelled amino acid incorporated is comparable to that obtained in the con trol assay without antibiotic. Little but sig nificant inhibitory activity is found with 3-monoacetoxy-chloramphenicol; this result is confirmed by the minimal inhibitory con centration (MIC) determinations [5].…”

“…It is generally recognized that most of these plasmids con fer to the bacteria the ability of destroying or inactivating antibiotics [6], For chloram phenicol, it has been shown that wild type strains of resistant Escherichia coli carrying R factors are able to synthetize a specific acetylase inactivating the drug [3,4,7]; the antibiotic is acetylated mainly in position 1 and 3 (1,3-diacetoxy-dcrivative) or in posi tion 3 (3-monoacetoxy-derivative), and, to a lower extent, in position 1 (1-monoacetoxyderivative) [4,8], Chloramphenicol binds to the 50 S subunits of the ribosome, probably inhibiting peptide bond formation [2,11,13], Preliminary investigations on the effect a wild type Escherichia coli strain carrying None of the acetylated derivatives has been of the 3-monoacetoxy-derivative and the 1,3-diacetoxy-derivative showed that the latter compound has no activity in vivo or in vitro, whereas the former has little inhibi tory.activity [5].…”

Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions

“…Our failure can be explained by a more recent crystallographic study conducted in E. coli ribosome [ 19 ]; the new orientation of CAM is rotated by 180°, thus directing the OH group in position 3 of CAM away from U2506 ( Figure 4 B). Noteworthy, CAM efficacy is decreased by mono-acetylation (compound 17 ) and nearly disappeared with di-acetylation (compound 18 ) [ 85 ].…”