Naphthoquinone-derivative as a synthetic compound to overcome the antibiotic resistance of methicillin-resistant S. aureus.
Commun Biol
; 3(1): 529, 2020 09 24.
Article
en En
| MEDLINE
| ID: mdl-32973345
ABSTRACT
The treatment of Staphylococcus aureus (S. aureus) infections has become more difficult due to the emergence of multidrug resistance in the bacteria. Here, we report the synthesis of a lawsone (2-hydroxy-1,4-naphthoquinone)-based compound as an antimicrobial agent against methicillin-resistant S. aureus (MRSA). A series of lawsone-derivative compounds were synthesized by means of tuning the lipophilicity of lawsone and screened for minimum inhibitory concentrations against MRSA to identify a candidate compound that possesses a potent antibacterial activity. The identified lawsone-derivative compound exhibited significantly improved drug resistance profiles against MRSA compared to conventional antibiotics. The therapeutic efficacy of the compound was validated using murine models of wound infection as well as non-lethal systemic infection induced by MRSA. Our study further revealed the multifaceted modes of action of the compound, mediated by three distinctive mechanisms (1) cell membrane damage, (2) chelation of intracellular iron ions, and (3) generation of intracellular reactive oxygen species.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones Estafilocócicas
/
Naftoquinonas
/
Staphylococcus aureus Resistente a Meticilina
/
Antibacterianos
Límite:
Animals
Idioma:
En
Revista:
Commun Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos