TY - JOUR
T1 - 5-O-Mycaminosyltylonolide antibacterial derivatives
T2 - Design, synthesis and bioactivity
AU - Sugawara, Akihiro
AU - Maruyama, Hitomi
AU - Shibusawa, Sho
AU - Matsui, Hidehito
AU - Hirose, Tomoyasu
AU - Tsutsui, Ayumi
AU - Froyman, Robrecht
AU - Ludwig, Carolin
AU - Koebberling, Johannes
AU - Hanaki, Hideaki
AU - Kleefeld, Gerd
AU - Omura, Satoshi
AU - Sunazuka, Toshiaki
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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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U2 - 10.1038/ja.2017.61
DO - 10.1038/ja.2017.61
M3 - Article
C2 - 28559578
AN - SCOPUS:85026416529
SN - 0021-8820
VL - 70
SP - 878
EP - 887
JO - Journal of Antibiotics
JF - Journal of Antibiotics
IS - 8
ER -