Planta Med 2012; 78 - PH26
DOI: 10.1055/s-0032-1320685

in vitro phase I metabolism and approach to the distribution of annonacin, a neurotoxic annonaceous acetogenin

J Le Ven 1, I Schmitz-Afonso 2, N Bonneau 1, T Cresteil 3, B Akagah 4, G Lewin 1, A Brunelle 2, D Touboul 2, P Champy 1
  • 1Université Paris-Sud, Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France
  • 2Equipe spectrométrie de masse
  • 3Métabolisation des Xénobiotiques, Centre de recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, avenue de la terrasse, 91198 Gif-sur-Yvette Cedex, France
  • 4Métabolisation Biomimétique, alpha-chimica, Châtenay-Malabry, France, 5, rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France

Annonacin is a prototypical Annonaceous acetogenin and is proposed as an environmental neurotoxin responsible for Guadeloupean atypical Parkinsonism, via consumption of fruits of Annona muricata L. (soursop). The molecule induces neurodegeneration in several rodent models. Phase 1 metabolism of annonacin was determined in vitro, using Rat and Human microsomes. Three metabolites were only identified in the latter, and were semisynthetized by porphyrin-catalyzed oxygenation, so as to allow their structural identification. A method for purification of annonacin from plasma, and subsequent determination using LC-ESI-Q3 is also proposed.