Four ardeemin analogs from endophytic Aspergillus fumigatus SPS-02 and their reversal effects on multidrug-resistant tumor cells.
Chem Biodivers
; 11(1): 85-91, 2014 Jan.
Article
en En
| MEDLINE
| ID: mdl-24443428
Four ardeemin derivatives, 5-N-acetylardeemin (1), 5-N-acetyl-15bß-hydroxyardeemin (2), 5-N-acetyl-15b-didehydroardeemin (3), and 5-N-acetyl-16α-hydroxyardeemin (4), were isolated from the fermentation broth of an endophytic Aspergillus fumigatus SPS-02 associated with Artemisia annua L. The structures of these metabolites were elucidated by a combination of spectroscopic data, including 1D-, 2D-NMR and MS. In vitro chemosensitization assay indicated that these ardeemins had different activities of reversing the multidrug-resistant (MDR) phenotype in three cancer cell lines, leukemia doxorubicin resistant cell K562/DOX, human lung adenocarcinoma cis-platin-resistant cell A549/DDP, and ovarian cancer cisplatin-resistant cell SK-OV-S/DDP. Compound 4 exhibited the strongest MDR reversing effect at 5â
µM concentration in K562/DOX and A549/DDP cell lines 5.2±0.18-fold, 8.2±0.23-fold, respectively, while compound 2 had the highest reversal capacity in SK-OV-S/DDP cell line with 10.8±0.28 fold. Preliminary investigation of their structureactivity relationship suggested that a OH group at C(15b) or C(16) in ardeemin plays a key role in reversing the MDR effect. It is the first report on ardeemin analogs from endophytic A. fumigatus with reversal effects on MDR cancer cell lines K562/DOX, A549/DDP and SK-OV-S/DDP.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Aspergillus fumigatus
/
Resistencia a Múltiples Medicamentos
/
Resistencia a Antineoplásicos
/
Alcaloides Indólicos
/
Neoplasias
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
Chem Biodivers
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article