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

The Retro-1 molecule was identified in a high-throughput screening as an inhibitor of ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. In order to improve the activity of Retro-1, a SAR study was undertaken yielding an analog that possesses roughly 70-fold better EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.