title: (S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived Compounds against Toxins.
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.
authors.affiliation: CEA, iBiTec-S/SIMOPRO, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Neetu
authors.initials: N
authors.lastname: Gupta
authors.affiliation: CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pons
authors.affiliation: CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Noël
authors.affiliation: CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Buisson
authors.affiliation: CEA, iBiTec-S/SIMOPRO, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Michau
authors.affiliation: 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.
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.affiliation: CEA, iBiTec-S/SIMOPRO, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gillet
authors.affiliation: CEA, iBiTec-S/SIMOPRO, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Barbier
authors.affiliation: CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cintrat
keywords: Retro-2.1; Shiga toxin; dihydroquinazolinones; ricin