Synthesis and antitumor activity of α,ß-unsaturated carbonyl moiety- containing oleanolic acid derivatives targeting PI3K/AKT/mTOR signaling pathway.
Bioorg Chem
; 101: 104036, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32629283
Oleanolic acid (OA) and its semi-synthetic derivatives have been reported to have a wide range of biological activities. The introduction of electrophilic Michael acceptor group can increase the reactivity of OA to cellular targets and thus improve the anti-tumor activity. In this work, a series of novel α,ß-unsaturated carbonyl derivatives of OA were designed and synthesized. Their in vitro cytotoxic activity against MCF-7, HepG2 and HeLa cells were tested. Most derivatives exhibited improved cell growth inhibitory activity, especially for 3d with an IC50 of 0.77 µM in MCF-7 cells. Moreover, 3d inhibited the migration of MCF-7 and HeLa cells at the concentration of 4 µM. Flow cytometric analysis revealed that 3d induced cell apoptosis and S phase arrest in a concentration-dependent manner. Western blotting experiment demonstrated that 3d inhibited the phosphorylation of AKT and mTOR. These results suggest that this series of OA derivatives bearing exocyclic methylene ketone pharmacophore are promising anticancer agents as potential PI3K/AKT/mTOR pathway inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Oleanólico
/
Fosfatidilinositol 3-Quinasas
/
Proteínas Proto-Oncogénicas c-akt
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2020
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos