alexa Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Zhan J, Burns AM, Liu MX, Faeth SH, Gunatilaka AA

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Abstract Wound-healing assay-guided fractionation of an EtOAc extract of the fungal strain Fusarium oxysporum EPH2RAA endophytic in Ephedra fasciculata afforded beauvericin (1), (-)-oxysporidinone (2), and two new N-methyl-2-pyridones, (-)-4,6'-anhydrooxysporidinone (3) and (-)-6-deoxyoxysporidinone (4). Beauvericin (1) inhibited migration of the metastatic prostate cancer (PC-3M) and breast cancer (MDA-MB-231) cells and showed antiangiogenic activity in HUVEC-2 cells at sublethal concentrations. Cytotoxicity-guided fractionation of an EtOAc extract of F. oxysporum strain CECIS occurring in Cylindropuntia echinocarpus afforded rhodolamprometrin (5), bikaverin (6), and the new natural product 6-deoxybikaverin (7). All compounds were evaluated for cytotoxicity in a panel of four sentinel cancer cell lines, NCI-H460 (non-small-cell lung), MIA Pa Ca-2 (pancreatic), MCF-7 (breast), and SF-268 (CNS glioma), and only beauvericin (1) and bikaverin (6) were active, with 1 and 6 showing selective toxicity toward NCI-H460 and MIA Pa Ca-2, respectively. Interestingly, 6-deoxybikaverin (7) was completely devoid of activity, suggesting the requirement of the C-6 hydroxy group of bikaverin for its cytotoxic activity.
This article was published in J Nat Prod and referenced in Pharmaceutica Analytica Acta

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