N‑Methyldihydroquinazolinone Derivatives of Retro‑2 with Enhanced Efficacy against Shiga Toxin
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...
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Published in | Journal of medicinal chemistry Vol. 56; no. 8; pp. 3404 - 3413 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
25.04.2013
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm4002346 |