title: Indole alkaloids from Fischerella inhibit vertebrate development in the zebrafish (Danio rerio) embryo model.
abstract: Cyanobacteria are recognized producers of toxic or otherwise bioactive metabolite associated, in particular, with so-called "harmful algal blooms" (HABs) and eutrophication of freshwater systems. In the present study, two apparently teratogenic indole alkaloids from a freshwater strain of the widespread cyanobacterial genus, Fischerella (Stigonemataceae), were isolated by bioassay-guided fractionation, specifically using the zebrafish (Danio rerio) embryo, as a model of vertebrate development. The two alkaloids include the previously known 12-epi-hapalindole H isonitrile (1), and a new nitrile-containing variant, 12-epi-ambiguine B nitrile (2). Although both compounds were toxic to developing embryos, the former compound was shown to be relatively more potent, and to correlate best with the observed embryo toxicity. Related indole alkaloids from Fischerella, and other genera in the Stigonemataceae, have been widely reported as antimicrobial compounds, specifically in association with apparent allelopathy. However, this is the first report of their vertebrate toxicity, and the observed teratogenicity of these alkaloids supports a possible contribution to the toxicity of this widespread cyanobacterial family, particularly in relation to freshwater HABs and eutrophication.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA. berryj@fiu.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Walton
authors.affiliation: Department of Biological Sciences, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. gantarm@fiu.edu.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Gantar
authors.affiliation: Division of Marine Biology and Fisheries, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33146, USA. pgibbs@rsmas.miami.edu.
authors.forename: Patrick D L
authors.initials: PD
authors.lastname: Gibbs
authors.affiliation: Division of Marine Biology and Fisheries, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33146, USA. mschmale@rsmas.miami.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Schmale
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA. berryj@fiu.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Berry
mesh_terms: D000818:Animals; D001681:Biological Assay; D000458:Cyanobacteria / Q000737:chemistry*; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D005618:Fresh Water / Q000382:microbiology; D057097:Harmful Algal Bloom; D026121:Indole Alkaloids / Q000633:toxicity*; D015394:Molecular Structure; D015027:Zebrafish / Q000196:embryology*
chemical_list: D026121:Indole Alkaloids