Synthesis and biological evaluation of novel 1,2,3,4-tetrahydro-ß-carboline derivatives as potential antibacterial agents.
Bioorg Med Chem Lett
; 109: 129822, 2024 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-38823728
ABSTRACT
The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carbolinas
/
Pruebas de Sensibilidad Microbiana
/
Bacterias Gramnegativas
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Bacterias Grampositivas
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Antibacterianos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China