Structure determination and cytotoxic evaluation of metabolites from the entomogenous fungus Fusarium equiseti

• Published in: Journal of antibiotics 2021-03, Vol.74 (3), p.176-180
• Main Authors: Liu, Shasha, Gao, Wenbin, Yang, Xiaohui, Huo, Ruiyun, Chen, Fengli, Cao, Fei, Luo, Duqiang
• Format: Article
• Language: English
• Subjects: 101/1; 101/58; 101/6; 631/535/878; 631/92/349; Antibiotics; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Cancer; Cytotoxicity; Flow cytometry; Fungi; Life Sciences; Medicinal Chemistry; Metabolites; Microbiology; Natural products; Organic Chemistry; X-ray diffraction
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-020-00379-x

Investigation of the entomogenous fungus Fusarium equiseti LGWB-9 from Harmonia axyridis led to the isolation of fusarisetin B ( 2 ) and its analog, fusaketide A ( 1 ), along with two known compounds ( 3 and 4 ). Among them, fusaketide A ( 1 ) represent the first example of natural polyketide carbon skeleton with a [6/6/5/5] tetracyclic ring system. The planar structure and relative configuration of 1 was established on the basis of NMR spectroscopic data and 13 C NMR chemical shift calculation. The absolute configuration of 1 was assigned by quantum chemical TDDFT calculation of its ECD spectrum and single-crystal X-ray diffraction analysis using Cu Kα radiation. Compounds 1 and 2 showed cytotoxicities against MCF-7, MGC-803, HeLa and Huh-7 cell lines with the IC 50 values ranging from 2.4 to 69.7 μg ml −1 . Cell invasion, migration, DAPI staining, and flow cytometry experiments were carried out to examine the effect of 2 against MGC-803 cells. Western blot results showed that 2 could induce MGC-803 apoptosis through up-regulation of Bax and down-regulation of Bcl-2.