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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzodiazepinones / chemistry*
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Benzodiazepinones / pharmacology*
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Golgi Apparatus / drug effects
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Golgi Apparatus / metabolism
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HeLa Cells
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Humans
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Protein Transport / drug effects
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Protein Transport / physiology
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Shiga Toxins / antagonists & inhibitors*
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Shiga Toxins / metabolism
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Structure-Activity Relationship
Substances
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7-bromo-5-phenyl-4-propionyl-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one
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Benzodiazepinones
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Shiga Toxins