title: Identification of cytotoxic principles from Fusarium avenaceum using bioassay-guided fractionation.
abstract: The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum.
authors.affiliation: Department of Chemistry, National Veterinary Institute, P.O. Box 8156 Dep., N-0033 Oslo, Norway. silvio.uhlig@vetinst.no
authors.forename: Silvio
authors.initials: S
authors.lastname: Uhlig
authors.forename: Arno C
authors.initials: AC
authors.lastname: Gutleb
authors.forename: Ulf
authors.initials: U
authors.lastname: Thrane
authors.forename: Arne
authors.initials: A
authors.lastname: Flåøyen
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry; D002457:Cell Extracts / Q000633:toxicity*; D002460:Cell Line; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D003503:Cyclobutanes / Q000737:chemistry; D047630:Depsipeptides / Q000737:chemistry / Q000633:toxicity*; D005670:Fusarium / Q000737:chemistry*; D008660:Metabolism / Q000187:drug effects*; D010078:Oxazines; D011753:Pyrones / Q000737:chemistry; D034421:Sus scrofa; D014966:Xanthenes
chemical_list: D000935:Antifungal Agents; D002457:Cell Extracts; D003503:Cyclobutanes; D047630:Depsipeptides; D010078:Oxazines; D011753:Pyrones; D014966:Xanthenes; C100264:enniatins; C048670:antibiotic Y; C065449:chlamydosporal; C005843:resazurin; C008539:moniliformin