antibiotic, but because it can cause fatal blood dyscrasias(i.e., bone marrow suppression
and failure) its use is largely restricted to microorganisms that cannot be well controlled by
other antibiotics. Thus, it has been the drug of choice against typhoid. Chloramphenicol
binds to the 50S subunit of the ribosome and inhibits the enzyme peptidyl transferase. This
blocks peptide-bond formation between the amino acid-tRNA on the aminoacyl site and
the growing peptide chain on the peptidyl site of the ribosome, interrupting translation.
9.4.3.4 Antibacterials Targeting the Ribosomal 50S Subunit: Macrolides
The macrolides are a group of chemically related compounds isolated from the actino-
mycetes microorganism. Macrolides bind selectively to a specific site on the 50S ribo-
somal subunit, preventing the translocation step of bacterial protein synthesis.
Currently, more than 40 macrolide compounds with antibacterial properties have been
identified. Chemically, all macrolide antibacterials share three common features: a large
lactone ring, a glycosidically linked amino sugar, and a ketone group; the lactone ring
usually has 12, 14, or 16 atoms and is frequently unsaturated. Erythromycin (9.83) is
the most widely used macrolide; oleandomycin (9.84) has also been employed clinically
over the years. More recently, semisynthetic erythromycin analogs (clarithromycin
(9.85), azithromycin (9.86)) have demonstrated enhanced acid stability, improved
bioavailability, and superior pharmacokinetics. Erythromycin acts in a similar way to
chloramphenicol and can actually compete with chloramphenicol for the same binding
site. It is a nontoxic macrocyclic lactone, widely used against penicillin-resistant
Staphylococcusstrains, and is the drug of choice to cure Legionnaires’ disease, caused
byLegionella pneumophila. Gastrointestinal discomfort is a common side effect of the
macrolides.
9.4.3.5 Antibacterials Targeting the 50S Ribosomal Subunit: Lincomycins
Lincomycins are similar to macrolides in biochemical mechanism of action and
antibacterial spectrum of activity. They are sulphur-containing antibacterials, first
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