Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens.
Future Microbiol
; 18: 625-638, 2023 07.
Article
em En
| MEDLINE
| ID: mdl-37347211
ABSTRACT
Aim:
The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance.Methods:
We investigated the activity of RBx 10080758 against Gram-positive bacteria in vitro and in vivo.Results:
RBx 10080758 showed a potent 50% inhibitory concentration of 0.13 µM and 0.25 µM against gyrase B and topoisomerase IV, respectively, and exhibited strong whole-cell in vitro activity with MIC ranges of 0.015-0.06 and 0.015-0.03 µg/ml against Staphylococcus aureus and Streptococcus pneumoniae, respectively. In a rat thigh infection model with methicillin-resistant S. aureus, RBx 10080758 at 45 mg/kg exhibited a >3 log10 CFU reduction in thigh muscles.Conclusion:
RBx 10080758 displayed potent activity against multiple multidrug-resistant Gram-positive bacteria with a dual-targeting mechanism of action.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Topoisomerase IV
/
Staphylococcus aureus Resistente à Meticilina
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article