Cytotoxic Alkaloids Isolated from the Mangrove Endophytic FungusAspergillus fumigatus BF18

Introduction: HPLC analysis indicated that the mangrove endophytic fungus Aspergillus fumigatus BF-18 exhibited an abundant profile of secondary metabolites. To isolate and identify secondary metabolites from the culture extract of the fungus Aspergillus fumigatus BF-18, and evaluate the cytotoxic activity of these isolates. Methods: The strain Aspergillus fumigatus BF-18 was fermented statically using rice solid medium and extracted with MeOH. The extract was purified by silica gel and Sephadex LH-20 gel column chromatography, followed by semi-preparative HPLC. The structures of the isolated compounds were identified by analyses of ESI-MS and NMR spectroscopic data. The cytotoxic activities of the isolates were assayed using the MTT method. Results: Nine alkaloid compounds (1-9) were identified, including a new indole-quinoline alkaloid named chaetominine B (1). In MTT bioassays, pseurotin G (8) significantly inhibited the proliferation of non-small-cell lung cancer cell lines H1299 with an IC50 value of 1.1 μM. Discussion: Previous reports revealed that chaetominine (2) inhibited human leukemia K562 and colon cancer SW1116 cell growth at the nanomolar level. However, in this work, chaetominine (2) only exhibited weak anti-proliferative activity against H1299 and A549 cells, indicating that its antitumor activity is highly selective. Conclusion: The endophytic fungus Aspergillus fumigatus BF-18 isolated from mangroves produces cytotoxic alkaloid secondary metabolites with diverse chemical frameworks. The isolation and identification of the new compound 1 enriches the chemical diversity of indole-quinazoline alkaloids.