Bacteria-derived macrolides

Like tetracyclines, macrolides are also polyketides that are isolated from bacteria and inhibit protein synthesis in certain bacteria. Erythromycin (A.32) is the original macrolide (Figure A.9). Clarithromycin (Biaxin, A.33) and azithromycin (Zithromax, A.34) are semisynthetic derivatives of erythromycin. 

R Okamoto, H Nomura, M Tsuchiya, H Tsunekawa, T Fukumoto, T Inui, T Sawa, T Takeuchi, H Umezawa. The activity of 4"-<9-acylated tylosin derivatives against macrolide-resistant Gram-positive bacteria. J Antibiot 32 542-544, 1979. 

An interesting exception to the absolute validity of the tifth postulate is the considerable activity of chloramphenicol derivatives in cell-free model systems of protein synthesis when these derivatives are substituted with amino acyl residues instead of with dichloroacetyl as is the antibiotic itself (rev. in 2°)). This has been traced to the necessity of the dichloroacetyl grouping in aiding in the permeation of the antibiotic through the bacterial envelope 21 The amino acyl derivatives have very low antibacterial activity 20. Permeation failures of actinomycin D, macrolides and distamycin A with respect to certain families of bacteria occlude the action of these antibiotics on their intracellular drug receptors and target reactions but can be overcome experimentally by measures which render test organisms permeable. 

Tilmicosin, Figure 1, is a new semisynthetic antibiotic derived from the macrolide antibiotic tylosin. The synthesis and antibacterial activity of tilmicosin have been described by Debono, et al. and Kirst, et al. (/-4). Tilmicosin has in vitro activity against a variety of Gram positive and Gram negative bacteria, as well as mycoplasma species. It is effective for treatment of bovine respiratory disease caused by Pasteurella haemolytica when administered as a single subcutaneous injection (5, 6). This paper describes the excretion, tissue residue pattern, and metabolism of tilmicosin when injected into cattle, and also gives comparative metabolism data from rats which were dosed orally. 

Erythromycin A, the major fermentation component of S. erythraea, is a 14-membered ring macrolide that is used by medicinal chemists as the foundation for building semisynthetic derivatives of erythromycin antibiotics. (Macrohdes inhibit bacteria by interfering with microbial protein biosynthesis.) Semisynthetic macrolides are popular with clinicians because they can be administered orally and have relatively low toxicity. They are often used to treat respiratory tract infections, and have been especially effective against conditions such as Legionnaires disease and community-acquired pneumonia. Erythromycin therapy is often prescribed for individuals allergic to penicillin. One of the most widely used macrohde antibiotics... 

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