Design, semi-synthesis and bioevaluation of koumine-like derivatives as potential antitumor agents in vitro and in vivo.
Future Med Chem
; 16(14): 1413-1428, 2024.
Article
en En
| MEDLINE
| ID: mdl-39190473
ABSTRACT
Aims:
Five series of novel koumine-like compounds were designed, semi-synthesized and systematically evaluated for antitumor activities.Methods:
All compounds were evaluated for antiproliferative activity against four human cancer cell lines, including HT-29, HCT-116, HCT-15 and Caco-2.Results:
Most compounds exhibited much higher antiproliferation activities (IC50 <10 µM) than koumine. Two selected compounds A4 and C5 showed comparable antitumor effects to 5-FU in vivo, as well as better safety profiles. Further studies suggested that A4 and C5 could arrest HT-29 cell cycle in G2 phase and raise reactive oxygen species level, thus inducing cell apoptosis related to Erk MAPK and NF-κB signaling pathways inhibition.Conclusion:
These results will greatly promote the druggability study of these koumine-like compounds.
[Box see text].
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ensayos de Selección de Medicamentos Antitumorales
/
Diseño de Fármacos
/
Apoptosis
/
Proliferación Celular
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China