Four Ardeemin Analogs from Endophytic Aspergillus fumigatus SPS‐02 and Their Reversal Effects on Multidrug‐Resistant Tumor Cells

Four ardeemin derivatives, 5‐N‐acetylardeemin ( 1 ), 5‐N‐acetyl‐15bβ‐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 5 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.