Cytotoxic alkaloids from the marine shellfish-associated fungus Aspergillus sp. XBB-4 induced by an amino acid-directed strategy

Eight different culture media were used to culture shellfish Panopea abbreviate associated fungus Aspergillus sp. XBB-4. In a glucose-peptone-yeast (GPY) culture medium supplied with amino acids, this fungus can produce chemodiversity metabolites. Four new alkaloids including three β-carboline alkaloids, aspercarbolines A–C (1–3) and one piperazinedione, asperdione A (13) along with nine known compounds were isolated. The structures were elucidated mainly based on the NMR, MS, ECD and X-ray single-crystal diffraction data. The possible biosynthetic pathways of aspercarbolines A–C (1–3) were proposed. All compounds (1–13) were evaluated for their cytotoxicity against six cancer cell lines, including human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and SUNE1, and human hepatocellular carcinoma cell lines hepG2 and QGY7701.