Discovery of potent natural product higenamine derivatives as novel Anti-Fusobacterium nucleatum agents.
Bioorg Chem
; 138: 106586, 2023 09.
Article
en En
| MEDLINE
| ID: mdl-37178651
ABSTRACT
Fusobacterium nucleatum (F. nucleatum) is closely associated with the occurrence and development of colorectal cancer (CRC). Discovery of specific antibacterial agents against F. nucleatum was urgent for the prevention and treatment of CRC. We screened a natural product library and successfully identified higenamine as an antibacterial hit against F. nucleatum. Further hit optimizations led to the discovery of new higenamine derivatives with improved anti-F. nucleatum activity. Among them, compound 7c showed potent antibacterial activity against F. nucleatum (MIC50 = 0.005 µM) with good selectivity toward intestinal bacteria and normal cells. It significantly inhibited the migration of CRC cells induced by F. nucleatum. Mechanism study revealed that compound 7c impaired the integrity of biofilm and cell wall, which represents a good starting point for the development of novel anti-F. nucleatum agents.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2023
Tipo del documento:
Article
País de afiliación:
China