AUTHOR=Song Wei , Ji Lianlian , Zhang Yanxia , Cao Longhe 

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

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1400803

DOI=10.3389/fmicb.2024.1400803

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Penicillium oxalicum</italic> 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B (<bold>1</bold>) and peniochroloid B (<bold>5</bold>), as well as four related derivatives (compounds <bold>2</bold>–<bold>4</bold> and <bold>6</bold>). The chemical structures of these compounds, including the absolute configurations of <bold>1</bold> and <bold>5</bold>, were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound <bold>1</bold> 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. <italic>In vitro</italic> cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that <bold>1</bold> strongly inhibited the FADU cell line, with an IC<sub>50</sub> value of 0.43 ± 0.03 μM. This study suggested that the new prenylated indole alkaloid <bold>1</bold> is a potential lead compound for anti-FADU drugs.</p>