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.
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.