Search for Cell Motility and Angiogenesis Inhibitors with Potential Anticancer Activity: Beauvericin and Other Constituents of Two Endophytic Strains of Fusarium oxysporum

摘要

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 anti-angiogenic 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 carcinoma), 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.