Title: Aflaquinolones A-G: Secondary metabolites from marine and fungicolous isolates of Aspergillus spp. Authors
|Neff, Scott -|
|Lee, Sang Un -|
|Asami, Yukihiro -|
|Ahn, Jong Seog -|
|Oh, Hyuncheol -|
|Baltrusaitis, Jonas -|
|Gloer, James -|
Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 23, 2012
Publication Date: March 23, 2012
Citation: Neff, S.A., Lee, S., Asami, Y., Ahn, J., Oh, H., Baltrusaitis, J., Gloer, J.B., Wicklow, D.T. 2012. Aflaquinolones A-G: Secondary metabolites from marine and fungicolous isolates of Aspergillus spp. Journal of Natural Products. 75(3):464-472. Interpretive Summary: Fungi produce a wide variety of bioactive compounds of importance to agriculture, medicine, and industrial production. Our previous inestigations demonstrated that fungi capable of parasitizing and killing other fungi offer a potential source of novel antifungal compounds. In the current study a previously undescribed species of Aspergillus, encountered as a colonist and potential parasite of a wood decay fungus collected in an ‘Alien’ Wet Forest, Hawaii, was examined for its ability to produce antifungal agents and other bioactive metabolites. Extracts from this isolated showed antifungal activity against mycotoxigenic and pathogenic fungi, Aspergillus flavus and Fusarium verticillioides, and slowed the growth of fall armyworm. In addition, we identified several novel aflaquinolones, which are reported as new metabolites with cytotoxic activity against five cancer cell lines. The discovery of metabolites with cytotoxic effects, and the demonstration of the production of known metabolites exhibiting antifungal activity by a new species of Aspergillus will serve to guide the synthesis of antibiotics and fungicides important to agriculture with additional potential for discovery of chemistry with medically relevant biological effects.
Technical Abstract: Seven new compounds (aflaquinolones A-G; 1-7) containing dihydroquinolin-2-one and terpenoid units have been isolated from two different fungal sources. Two of these metabolites (1 and 2) were obtained from a Hawaiian fungicolous isolate of Aspergillus sp. (section Flavipedes; MYC-2048=NRRL 58570), while the others were obtained from a marine Aspergillus isolate (SF-5044) collected in Korea. The structures of these compounds were determined mainly by analysis of NMR and MS data. Relative and absolute configurations were assigned on the basis of NOESY data and 1H NMR J-values, comparison of calculated and experimental ECD spectra, and analysis of a Mosher ester derivative of 2. Several known compounds, including alantrypinone, aspochalasins I and J, methyl-3, 4, 5-trimethoxy-2((2-((3-pyridinylcarbonyl)amino) benzoyl)amino)benzoate, and trans-dehydrocurvularin were also encountered in the extract of the Hawaiian isolate. The antifungal and antiinsectan activity observed in the original extract was attributed to these known metabolites, but several of the new compounds were found to display cytotoxicity.