Identification of novel phytotoxins from Australian range plants linked to severe mammalian digestive toxicity

We have used a digestive developmental in vivo zebrafish model to examine Australian rangeland plants for their involvement in specific digestive disorders in livestock. The model allows us to discover causative phytotoxins linked to a syndrome. Here, we report the isolation and structural elucidation of five isoflavonoid compounds 1-5 with specific biological activity. From the active fraction, we identified the causative phytotoxins as two novel isoflavonoids (1, 4), both with an unusual skeleton. In addition, we isolated an additional novel isoflavonoid (3), a novel pterocarpan derivative (5), and a known isoflavone, betavulgarin (2). Compound 4 contributed to the specific biological damage in the zebrafish. The compound is highly reactive and conjugates spontaneously with common nucleophilic biological molecules, indicating a strong electrophilic nature, suggesting a possible mechanism of action that explains death in the animals. The isolation and structural elucidation of 1- 5 , together with their biological data, will be presented.