Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzamides / pharmacology
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Biological Transport / drug effects
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Endosomes / drug effects
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Endosomes / metabolism
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HeLa Cells
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Humans
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Inhibitory Concentration 50
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Quinazolinones / chemical synthesis*
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Quinazolinones / pharmacology
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Shiga Toxin / antagonists & inhibitors*
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Shiga Toxin / metabolism
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Shiga Toxins / antagonists & inhibitors*
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Structure-Activity Relationship
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Thiophenes / pharmacology
Substances
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2-(((5-methyl-2-thienyl)methylene)amino)-N-phenylbenzamide
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Benzamides
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Quinazolinones
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Shiga Toxins
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Thiophenes
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Shiga Toxin