Biliatresone, a Reactive Natural Toxin from Dysphania glomulifera and D. littoralis: Discovery of the Toxic Moiety 1,2-Diaryl-2-Propenone

  • Chem Res Toxicol. 2015 Aug 17;28(8):1519-21. doi: 10.1021/acs.chemrestox.5b00227.
Kyung A Koo  1 ,  Kristin Lorent ,  Weilong Gong ,  Peter Windsor  2 ,  Stephen J Whittaker  3 ,  Michael Pack ,  Rebecca G Wells ,  John R Porter  1
Affiliations
  • 1. †Department of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania 19104, United States.
  • 2. ⊥Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales 2006, Australia.
  • 3. #Hume Livestock and Pest Authority, Albury, New South Wales Australia.
PMID: 26175131 DOI: 10.1021/acs.chemrestox.5b00227
Abstract

We identified a reactive natural toxin, biliatresone, from Dysphania glomulifera and D. littoralis collected in Australia that produces extrahepatic biliary atresia in a zebrafish model. Three additional isoflavonoids, including the known isoflavone betavulgarin, were also isolated. Biliatresone is in the very rare 1,2-diaryl-2-propenone class of isoflavonoids. The α-methylene of the 1,2-diaryl-2-propenone of biliatresone spontaneously reacts via Michael addition in the formation of water and methanol adducts. The lethal dose of biliatresone in a zebrafish assay was 1 μg/mL, while the lethal dose of synthetic 1,2-diaryl-2-propen-1-one was 5 μg/mL, suggesting 1,2-diaryl-2-propenone as the toxic Michael acceptor.

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