Biemamides A-E, Inhibitors of the TGF-β Pathway That Block the Epithelial to Mesenchymal Transition.
Fan ZhangDoug R BraunGene E AnanievF Michael HoffmannI-Wei TsaiScott R RajskiTim S BugniPublished in: Organic letters (2018)
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.
Keyphrases
- transforming growth factor
- induced apoptosis
- high resolution
- magnetic resonance
- epithelial mesenchymal transition
- high glucose
- cell cycle arrest
- molecular dynamics
- drug induced
- density functional theory
- molecular dynamics simulations
- single cell
- endothelial cells
- cell proliferation
- mass spectrometry
- endoplasmic reticulum stress
- pi k akt