Four ardeemin analogs from endophytic Aspergillus fumigatus SPS-02 and their reversal effects on multidrug-resistant tumor cells.

Abstract

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.

• Authors: Hua-Wei Zhang, Chen Ying, Yi-Fei Tang
• Journal: Chemistry & biodiversity (Chem Biodivers) Vol. 11 Issue 1 Pg. 85-91 (Jan 2014) ISSN: 1612-1880 [Electronic] Switzerland
• PMID: 24443428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

Chemical References

• Antineoplastic Agents, Phytogenic
• Indole Alkaloids
• ardeemin

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Aspergillus fumigatus (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Indole Alkaloids (chemistry, pharmacology)
• K562 Cells
• Molecular Conformation
• Neoplasms (drug therapy, pathology)
• Structure-Activity Relationship