New cytotoxic indole derivatives with anti-FADU potential produced by the endophytic fungus 2021CDF-3 through the OSMAC strategy.

Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for exploring chemically diverse secondary metabolites. In this study, continued chemical investigations of the marine red algae-derived endophytic fungus 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B () and peniochroloid B (), as well as four related derivatives (compounds - and ). The chemical structures of these compounds, including the absolute configurations of and , were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound was found to possess an unusual 3-pyrrolidone dimethylbenzopyran fused to the bicyclo[2.2.2]diazaoctane moiety, which was rare in previously reported prenylated indole alkaloids. cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that strongly inhibited the FADU cell line, with an IC value of 0.43 ± 0.03 μM. This study suggested that the new prenylated indole alkaloid is a potential lead compound for anti-FADU drugs.