AUTHOR=Xu An , Xu Xiang-Nan , Zhang Mi , Li Chun-Lian , Liu Li , Fu De-Yuan 

TITLE=Cytotoxic indole alkaloids and polyketides produced by a marine-derived fungus Aspergillus flavipes DS720

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.959754

DOI=10.3389/fmicb.2022.959754

ISSN=1664-302X

ABSTRACT=<p>Marine-derived microorganisms possess the unique metabolic pathways to produce structurally novel secondary metabolites with potent biological activities. In this study, bioactivity-guided isolation of the marine deep-sea-derived fungus <italic>Aspergillus flavipes</italic> DS720 led to the characterization of four indole alkaloids (compounds <bold>1</bold>–<bold>4</bold>) and four polyketides (compounds <bold>5</bold>–<bold>8</bold>), such as two new indoles, flavonoids A (<bold>1</bold>) and B (<bold>2</bold>) with a C-6 reversed prenylation, and a new azaphilone, flaviazaphilone A (<bold>5</bold>). Their chemical structures were unambiguously established by an extensive interpretation of spectroscopic data, such as 1D/2D NMR and HRESIMS data. The absolute configurations of the new compound <bold>5</bold> were solved by comparing the experimental and calculated Electronic Circular Dichroism (ECD) spectra. Since sufficient amount of flavonoids A (<bold>1</bold>) was obtained, <bold>1</bold> was subjected to a large-scale cytotoxic activity screening against 20 different human tumor cell lines. The results revealed that <bold>1</bold> showed broad-spectrum cytotoxicities against HeLa, 5637, CAL-62, PATU8988T, A-375, and A-673 cell lines, with the inhibition rates of more than 90%. This study indicated that the newly discovered indole alkaloid <bold>1</bold> may possess certain potential for the development of lead compounds in the future.</p>