Division of Pharmacy and Optometry, University of Manchester, Oxford Road, M13 9PT, Manchester, United Kingdom.
Division of Pharmacy and Optometry, University of Manchester, Oxford Road, M13 9PT, Manchester, United Kingdom.
Int J Antimicrob Agents. 2018 Mar;51(3):283-298. doi: 10.1016/j.ijantimicag.2017.05.020. Epub 2017 Jun 28.
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.
十六元大环内酯类抗生素（例如泰乐菌素 A 和交沙霉素）主要用于兽医领域，与基于十四元环和十五元环的红霉素类抗生素相比，其研究要少得多。尽管这些抗生素具有相似的抗菌谱，主要对革兰氏阳性菌和有限范围的革兰氏阴性菌有效，但十六元大环内酯类抗生素具有一些优势。它们包括更好的胃肠道耐受性、缺乏药物相互作用以及通过延长肽隧道的到达范围来增加与某些耐药菌的相互作用，从而具有活性。除了抗菌活性外，该类最著名的代表泰乐菌素 A 以及某些去甲霉醇（泰乐菌素 B）衍生物也表现出抗疟活性。十四元大环内酯类抗生素，如阿奇霉素、索利霉素和克林霉素也观察到了这种抗疟活性。本文综述了十六元大环内酯类抗生素的生物合成、结构、化学性质和作用模式的最新研究进展，特别强调了其最受关注的成员：泰乐菌素 A 和交沙霉素。
