Discovery of antitumor ursolic acid long-chain diamine derivatives as potent inhibitors of NF-κB.
Bioorg Chem
; 79: 265-276, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29778798
ABSTRACT
A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC50 values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 5.22 to 8.95⯵M. Moreover, compound 8c successfully suppressed the migration of A549 cells. Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-κB signalling pathway. Molecular docking study revealed that key interactions between 8c and the active site of NF-κB in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Triterpenos
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FN-kappa B
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Diaminas
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Descubrimiento de Drogas
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Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2018
Tipo del documento:
Article