Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents
Acta Pharmaceutica Sinica B
; (6): 222-228, 2016.
Article
Dans En
| WPRIM
| ID: wpr-309964
Responsable en Bibliothèque :
WPRO
ABSTRACT
Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
Texte intégral:
1
Indice:
WPRIM
langue:
En
Texte intégral:
Acta Pharmaceutica Sinica B
Année:
2016
Type:
Article