354815-09-1Relevant articles and documents
Potent and specific inhibitors of trypanothione reductase from Trypanosoma cruzi: Bis(2-aminodiphenylsulfides) for fluorescent labeling studies
Girault, Sophie,Davioud-Charvet, Elisabeth,Maes, Louis,Dubremetz, Jean-Francois,Debreu, Marie-Ange,Landry, Valerie,Sergheraert, Christian
, p. 837 - 846 (2001)
In order to optimise the activity of bis 2-aminodiphenylsulfides) upon trypanothione reductase TR) from Trypanosoma cruzi, a new series of bis 2-aminodiphenylsulfides) possessing three side chains was synthesized. Various moieties were introduced at the end of the third side chain, including acridinyl or biotinyl moieties for fluorescent labeling studies. TR inhibition was improved; the most potent inhibitor IC50=200 nM) was selective towards TR versus human glutathione reductase and corresponded to a single myristyl group. Compounds were also tested in vitro upon Trypanosoma cruzi and Leishmania infantum amastigotes, upon-Trypanosoma brucei trypomastigotes, and for their cytotoxicity upon human MRC-5 cells. In the presence of serum, acridine derivative was no longer detectable in mass spectrometry and its antitrypanosomal activity no longer observed. This transformation might explain the absence of correlation between the potent TR inhibition and the in vitro antiparasitic activity with both of the first generation of 2-aminodiphenylsulfides. Copyright
