A Potent and Narrow-Spectrum Antibacterial against Clostridioides difficile Infection.
J Med Chem
; 66(20): 13891-13899, 2023 10 26.
Article
em En
| MEDLINE
| ID: mdl-37732641
ABSTRACT
Clostridioides difficile is an anaerobic Gram-positive bacterium that colonizes the gut of patients treated with broad-spectrum antibiotics. The normal gut microflora prevents C. difficile colonization; however, dysbiosis by treatment with broad-spectrum antibiotics causes recurrent C. difficile infection (CDI) in 25% of patients. There are no fully effective antibiotics for multiple recurrent CDIs. We report herein that oxadiazole antibiotics exhibit bactericidal activity against C. difficile vegetative cells. We screened a library of 75 oxadiazoles against C. difficile ATCC 43255. The findings from this collection served as the basis for the syntheses of an additional 58 analogs, which were tested against the same strain. We report a potent (MIC50 = 0.5 µg/mL and MIC90 = 1 µg/mL values for 101 C. difficile strains) and narrow-spectrum oxadiazole (3-(4-(cyclopentyloxy)phenyl)-5-(4-nitro-1H-imidazol-2-yl)-1,2,4-oxadiazole; compound 57), which is not active against common gut bacteria or other tested organisms. Compound 57 is selectively bactericidal against C. difficile and targets cell-wall synthesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clostridioides difficile
/
Infecções por Clostridium
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2023
Tipo de documento:
Article