Antibacterial and Solubility Optimization of Thiomuracin A.
J Med Chem
; 59(14): 6920-8, 2016 07 28.
Article
em En
| MEDLINE
| ID: mdl-27355833
ABSTRACT
Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon- and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
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Tiazóis
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Clostridioides difficile
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Infecções por Clostridium
/
Antibacterianos
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2016
Tipo de documento:
Article
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA