Felim, Anne (1980-....).

Synthèse biomimétique d'adduits catéchol-thioéthers dérivés de la méthylènedioxyméthamphétamine à partir d'orthoquinone électrogénérée : leur implication dans la neurotoxicité de l'ecstasy by Anne Felim( Book )

2 editions published in 2009 in French and held by 2 WorldCat member libraries worldwide

ICV injection of MDMA (ecstasy) in rats fails to reproduce long-term toxic effects observed after peripheral administration. Therefore, systemic metabolites play a key role in the development of cytotoxicity. In humans, the major metabolite is 3,4-dihydroxymethamphetamine (HHMA), easily oxidizable to the orthoquinone species. This can further react with endogenous thiol derivatives, yielding quinol-thioether conjugates. In the first part of the thesis, a one pot synthesis of racemic catechol-thioether metabolites has been developed, using anodic oxidation as a mimic of enzymatic oxidation. In the second part, the synthesis of (R)-HHMA, precursor of the enantiomerically pure quinol-thioether adducts, is described starting from L-dopa (inducer of chirality). The third part reports the results of in vitro assays which show that some catechol-thioether conjugates can induce toxic effects leading to the formation of ROS, through redox cycling processes involving o-quinonoid species