neo-Clerodane diterpenoids from Scutellaria barbata mediated inhibition of P-glycoprotein in MCF-7/ADR cells.
Eur J Med Chem
; 121: 238-249, 2016 Oct 04.
Article
en En
| MEDLINE
| ID: mdl-27240278
ABSTRACT
Ten new (1-10) and seventeen known (11-27) neo-clerodane diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane diterpenoids on multidrug resistance were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 µM to 1.3 µM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane diterpenoids were also discussed.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Subfamilia B de Transportador de Casetes de Unión a ATP
/
Scutellaria
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Diterpenos de Tipo Clerodano
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2016
Tipo del documento:
Article