2. Academic Validation
  3. N-methyldihydroquinazolinone derivatives of Retro-2 with enhanced efficacy against Shiga toxin

N-methyldihydroquinazolinone derivatives of Retro-2 with enhanced efficacy against Shiga toxin

  • J Med Chem. 2013 Apr 25;56(8):3404-13. doi: 10.1021/jm4002346.
Romain Noel 1,  Neetu Gupta,  Valérie Pons,  Amélie Goudet,  Maria Daniela Garcia-Castillo,  Aurélien Michau,  Jennifer Martinez,  David-Alexandre Buisson,  Ludger Johannes,  Daniel Gillet,  Julien Barbier,  Jean-Christophe Cintrat
Affiliations

Affiliation

  • 1 CEA, iBiTec-S/SCBM, CEA-Saclay, LabEx LERMIT, F-91191 Gif-sur-Yvette, France.
PMID: 23517565 DOI: 10.1021/jm4002346
Abstract

The Retro-2 molecule protects cells against Shiga toxins by specifically blocking retrograde transport from early endosomes to the trans-Golgi network. A SAR study has been carried out to identify more potent compounds. Cyclization and modifications of Retro-2 led to a compound with roughly 100-fold improvement of the EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay. We also demonstrated that only one enantiomer of the dihydroquinazolinone reported herein is bioactive.

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