Fumagillin is a polyene natural product and mycotoxin isolated from Aspergillus fumigatus in 1951 as a potent antiprotozoan for agents that cause amoebiasis. More recently, Fumagillin has been shown to inhibit endothelial cell proliferation and angiogenesis in vitro. It is an amebicide and has antibiotic properties and has been used for studying honey bee infections under laboratory conditions. The mycotoxin is produced by enzymes encoded in a biosynthetic cluster located on chromosome 8 of A. fumigatus. Fumagillin is gaining popularity for potential use as a biomarker for invasive aspergillosis.
Fumagillin is soluble in ethanol, methanol, DMF or DMSO. Poor water solubility.
| Mechanism of Action | Fumagillin is a macrolide inhibits endothelial cell proliferation and angiogenesis by inhibiting methionine aminopeptidase-2 (MetAP-2) via covalent binding to the His231, inhibiting the proper functioning of the protein. and the compound and its derivatives are being considered in cancer research as an angiogenesis inhibitor. |
| Spectrum | fungi, parasites, HIV |
| Eukaryotic Cell Culture Applications |
In vitro effect of Fumagillin in cell culture with A549 pneumocytes saw the reduction of electron chain activity, migration, and proliferation. Fumagillin also affected viability of RAW 264.7 cells. This was the first study looking at the role of Fumagillin on A. fumigatus virulence and found the fungus has an intrinsic resistance to its own toxin (Garuceaga et al, 2021). In vitro research on aspergillosis prompted authors to discover the first validated method to quantify Fumagillin in cell culture media (RPMI-1640) using Solid Phase Extraction with Ultra High Performance Liquid Chromatrography coupled to a Diode Array Detection, or SPE-UHPLC-DAD) at 336 nm. The method was demonstrated to fullfill regulatory guidelines (EMA and FDA). Authors quantified Fumagillin from three different A. fumigatus strains This allows the application of microbiological studies and the study of toxin release during host-fungus interaction assays using cell lines but could also be used for other matrices like plasma, urine etc. Authors found it was important to use red light during the sample treatment since Fumagillin is subject to photodegradation (Gonzalez et al, 2021). |
| References |
Guruceaga X et al (2021) Aspergillus fumigatus Fumagillin contributes to host cell damage. J. Fungi 7(11):936 Griffith EC et al (1998) Molecular recognition of angiogenesis inhibitors Fumagillin and ovalicin by methionine aminopeptidase 2. PNAS 95(26):15183-15188 Higes M et al (2011) The stability and effectiveness of Fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis mellifera) under laboratory and field conditions. Apidologiei 42(3):364-377 Lefkove B et al (2007) Fumagillin:An anti-infective as a parent molecule for novel angiogenesis inhibitors. Expert Rev. Anti Infect. Ther. 5:573 McCowen MC et al (1951) Fumagillin (H-3), a new antibiotic with amebicidal properties. Science 23:202 Oskar González O et al (2021) A novel SPE-UHPLC-DAD method for the determination of Fumagillin produced by Aspergillus fumigatus in cell culture media. Microchem. J. 169:106605 van den Heever JP et al (2016) Evaluation of Fumagilin-B® and other potential alternative chemoterapies agaisnt Nosema ceranae-infected honeybees (Apis mellifera) in cage trial assays. Apidologie 47:617-630 |