Biemamides A–E, Inhibitors of the TGF‑β Pathway That Block the Epithelial to Mesenchymal Transition

Screening of a marine natural products library for inhibitors of TGF-β revealed five pyrimidinedione derivatives, biemamides A–E (1–5). The structures were determined by 2D NMR and HRMS experiments; absolute configurations were established by advanced Marfey’s analysis and ECD calculations. Biemamid...

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Bibliographic Details
Published in:Organic letters 2018-09, Vol.20 (18), p.5529-5532
Main Authors: Zhang, Fan, Braun, Doug R, Ananiev, Gene E, Hoffmann, F. Michael, Tsai, I-Wei, Rajski, Scott R, Bugni, Tim S
Format: Article
Language:English
Subjects:
Animals
Biological Products - chemistry
Biological Products - pharmacology
Caenorhabditis elegans - drug effects
Caenorhabditis elegans - growth & development
Caenorhabditis elegans - metabolism
Cell Line
Dose-Response Relationship, Drug
Epithelial-Mesenchymal Transition - drug effects
Humans
Pyrimidinones - chemistry
Pyrimidinones - pharmacology
Structure-Activity Relationship
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - metabolism
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Summary:Screening of a marine natural products library for inhibitors of TGF-β revealed five pyrimidinedione derivatives, biemamides A–E (1–5). The structures were determined by 2D NMR and HRMS experiments; absolute configurations were established by advanced Marfey’s analysis and ECD calculations. Biemamides A–E specifically inhibited in vitro TGF-β induced epithelial to mesenchymal transition in NMuMG cells. Additionally, using Caenorhabditis elegans, selected biemmamides were found to influence in vivo developmental processes related to body size regulation in a dose-dependent manner.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.8b01871