Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin

  • J Med Chem. 2020 Aug 13;63(15):8114-8133. doi: 10.1021/acs.jmedchem.0c00298.
Hajer Abdelkafi  1 ,  Aurélien Michau  2 ,  Valérie Pons  1 ,  Flora Ngadjeua  2 ,  Alexandra Clerget  2 ,  Lilia Ait Ouarab  1 ,  David-Alexandre Buisson  1 ,  David Montoir  1 ,  Lucie Caramelle  2 ,  Daniel Gillet  2 ,  Julien Barbier  2 ,  Jean-Christophe Cintrat  1
Affiliations
  • 1. Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SCBM, 91191 Gif-sur-Yvette, France.
  • 2. Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, 91191 Gif-sur-Yvette, France.
PMID: 32648758 DOI: 10.1021/acs.jmedchem.0c00298
Abstract

High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.