Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 56, Issue 8, Pages 3404-3413Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm4002346
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- French National Agency for Research (ANR) [ANR-11-BSV2-0018]
- CEA
- Agence Nationale de la Recherche (ANR) [ANR-11-BSV2-0018] Funding Source: Agence Nationale de la Recherche (ANR)
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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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