Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Products / chemistry
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Biological Products / pharmacology*
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / growth & development
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Caenorhabditis elegans / metabolism
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Cell Line
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Dose-Response Relationship, Drug
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Epithelial-Mesenchymal Transition / drug effects*
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Humans
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology*
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Structure-Activity Relationship
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Transforming Growth Factor beta / antagonists & inhibitors*
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Transforming Growth Factor beta / metabolism
Substances
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Biological Products
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Pyrimidinones
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Transforming Growth Factor beta