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

  • J Antibiot (Tokyo). 2017 Jul;70(8):878-887. doi: 10.1038/ja.2017.61.
Akihiro Sugawara  1 ,  Hitomi Maruyama  1 ,  Sho Shibusawa  1 ,  Hidehito Matsui  1 ,  Tomoyasu Hirose  1 ,  Ayumi Tsutsui  1 ,  Robrecht Froyman  2 ,  Carolin Ludwig  2 ,  Johannes Koebberling  2 ,  Hideaki Hanaki  1 ,  Gerd Kleefeld  2 ,  Satoshi Ōmura  1 ,  Toshiaki Sunazuka  1
Affiliations
  • 1. Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
  • 2. Bayer Animal Health GmbH, Leverkusen, Germany.
PMID: 28559578 DOI: 10.1038/ja.2017.61
Abstract

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.

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