2. Academic Validation
  3. (S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived Compounds against Toxins

(S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived Compounds against Toxins

  • ACS Med Chem Lett. 2013 Dec 4;5(1):94-7. doi: 10.1021/ml400457j.
Neetu Gupta 1,  Valérie Pons 2,  Romain Noël 2,  David-Alexandre Buisson 2,  Aurélien Michau 1,  Ludger Johannes 3,  Daniel Gillet 1,  Julien Barbier 1,  Jean-Christophe Cintrat 2
Affiliations

Affiliations

  • 1 CEA, iBiTec-S/SIMOPRO, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
  • 2 CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
  • 3 U1143 INSERM, 75005 Paris, France ; Institut Curie, Centre de Recherche, Chemical Biology of Membranes and Therapeutic Delivery, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.
PMID: 24900779 DOI: 10.1021/ml400457j
Abstract

This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of a new compound, named Retro-2.1, active against toxins by inhibiting intracellular trafficking via the retrograde route. The absolute configuration of the bioactive enantiomer has been assigned from X-ray diffraction to the (S)-enantiomer. To date, (S)-Retro-2.1 is the most potent molecule to counteract the cytotoxic potential of ricin and Shiga toxin, with EC50 values of 23 and 54 nM, respectively.

Keywords

Retro-2.1; Shiga toxin; dihydroquinazolinones; ricin.

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