Identification, Isolation, and Characterization of Developmental Toxins from the Cyanobacterium Fischerella 52-1 Using the Zebrafish (Danio rerio) Embryo Model

Abstract

Cyanobacteria, also known as blue-green algae, are known to produce a number of biologically active compounds. Extracts of cultured cyanobacteria isolated from South Florida sources were screened for possible developmental toxins using the zebrafish (Danio rerio) embryo as a model of vertebrate development. A strain of cyanobacteria, Fischerella 52-1, isolated from the Florida Everglades, was found to produce metabolites that caused a consistent developmental dysfunction in embryos exposed to lipophilic extract. Initial chemical characterization of the bioactive fraction identified a series of eight apparent indole-containing compounds. The two main components were purified using the zebrafish embryo model to guide the fractionation. Chemical characterization using 1- and 2-dimensional NMR, HESIMS, HRHESIMS, and IR determined that the two main compounds were the previously identified 12-epi-Hapalindole H Isonitrile, and a novel compound 12-epi-Ambiugine B Nitrile. The major contributor of the developmental defects detected in the zebrafish embryos was 12-epi-Hapalindole H Isonitrile.