16-membered macrolide antibiotics: a review

The 16-membered macrolide antibiotics (e.g. tylosin A and josamycin) are mainly used in veterinary medicine, and are much less studied than their 14- and 15-membered erythromycin-based cousins. Although these antibiotics have similar antibacterial profiles, with activity primarily against Gram-positive and a limited range of Gram-negative organisms, the 16-membered macrolides show some advantages. These include better gastrointestinal tolerance, lack of drug-drug interactions, and activity against certain resistant bacterial strains by extension of the peptide tunnel reach allowing additional interactions. In addition to antibacterial activity, the most famous representative of the class, tylosin A, as well as some derivatives of desmycosin (tylosin B), have shown antimalarial activity. Such activity has also been observed in the 14-membered macrolide antibiotics, azithromycin, solithromycin and clindamycin. This antimalarial activity provides the opportunity to investigate these drugs as cheap and effective antimalarials. This is an overview of the latest research on biosynthesis, structure, chemical properties and mode of action of 16-membered macrolides, with special emphasis on their most explored members: tylosin A and josamycin.