5-O-Mycaminosyltylonolide antibacterial derivatives: design, synthesis and bioactivity.

The Journal of antibiotics 2017 Jul

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Tylosin is a 16-membered macrolide broad-spectrum antibiotic that has an important role in veterinary medicine, active against Gram-positive and a restricted range of Gram-negative bacteria. We synthesized 15 types of tylosin-related derivatives by chemical modification and evaluated them against mastitis pathogens. Among them, 20-deoxy-20-{N-methyl-N-[1-(3-quinolyl)-1H-1,2,3-triazol-4-yl]methylamino}-5-O-mycaminosyltylonolide 2f and 20-deoxy-20-{N-benzyl-N-[1-(3-quinolyl)-1H-1,2,3-triazol-4-yl]methylamino}-5-O-mycaminosyltylonolide 2k were found to not only expand their antibacterial impact to include Gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, but also to retain or increase antibacterial activity against Gram-positive bacteria, such as Staphylococcus aureus and Streptococcus uberis in comparison with the parent tylosin.

Citation

Akihiro Sugawara, Hitomi Maruyama, Sho Shibusawa, Hidehito Matsui, Tomoyasu Hirose, Ayumi Tsutsui, Robrecht Froyman, Carolin Ludwig, Johannes Koebberling, Hideaki Hanaki, Gerd Kleefeld, Satoshi Ōmura, Toshiaki Sunazuka. 5-O-Mycaminosyltylonolide antibacterial derivatives: design, synthesis and bioactivity. The Journal of antibiotics. 2017 Jul;70(8):878-887