Structure–Activity Relationship Studies of Retro‑1 Analogues against Shiga Toxin

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...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2020-08, Vol.63 (15), p.8114-8133
Main Authors: Abdelkafi, Hajer, Michau, Aurélien, Pons, Valérie, Ngadjeua, Flora, Clerget, Alexandra, Ait Ouarab, Lilia, Buisson, David-Alexandre, Montoir, David, Caramelle, Lucie, Gillet, Daniel, Barbier, Julien, Cintrat, Jean-Christophe
Format: Article
Language:English
Subjects:
Life Sciences
Pharmaceutical sciences
Pharmacology
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.0c00298