Erythromycin position C11-C12. It also has imidazo-pyridyl
Erythromycin is a macrolide antibioticthat have a 14-membered lactone ring with cladinose.In oral administration,erythromycin is sufficiently absorbed from the gastrointestinal tract.If pH ofthe environment is low, for instance in the stomach, erythromycin falls intosome internal changes.After these changes some products are occured and theyhave no antimicrobial activity.
By replacing cladinose group ofmacrolides with a keto group, ketolides are obtained.Ketolides aresemisynthetic derivatives of macrolides. Telithromycin is a member of ketolidesand it has large aromatic N-substitued carbamate bridge at position C11-C12. It also has imidazo-pyridyl group attachmentin this ring and it has 6-O CH3 group.Due to these specific modifications,telithromycin has good activity on S.Pneumoniae and some gram-positive bacteries that have resistance toerytromycin.
On the other hand thesemodifications increases bioavailability and acid stability of molecule.4.MECHANISM of ACTIONBacterial ribosomes have 50S and 30Sribosomal subunits. Subunits of ribosome consist protein and rRNA. The smallsubunit of ribosome have an interaction with mRNA and translates the geneticcode. The large subunit shows function as a catalytic center, peptide bondsbetween aminoacids is formed in this unit.
The elongated peptide enters apeptide exit channel within the 50S ribosomal subunit.Ketolides and macrolides inhibit proteinsynthesis with the identical mechanism, . They bind within the exit tunnel ofthe 50S subunit, so blocks the exit of rising polypeptides.
23S rRNA have somespecific residues (A2058 and A2059) on domain V. Macrolides and ketolides bindthese residues. In addition, telithromycin is a veryeffective inhibitor of the translation function at the level of the 50Sribosomal subunit. Telithromycin binds to a specific residue (A752) on domainII of the 23S rRNA, via the 11,12 carbamate bridge containing the alkyl-arylextension.Due to the binding to domain II, binding efficiency of telithromycin to ribosomes is 10-fold more thanerytromycin.
Telithromycin can inhibit the formation of small ribosomal subunitand it can inhibit assembly of the large ribosomal subunit.