Chemical Investigation of Diketopiperazines and N-Phenethylacetamide Isolated from <i>Aquimarina</i> sp. MC085 and Their Effect on TGF-β-Induced Epithelial–Mesenchymal Transition

Abstract

Chemical investigations of Aquimarina sp. MC085, which suppressed TGF-β-induced epithelial–mesenchymal transition (EMT) in A549 human lung cancer cells, led to the isolation of compounds 1–3. Structural characterization using spectroscopic data analyses in combination with Marfey’s analysis revealed that they were two diketopiperazines [cyclo(l-Pro-l-Leu) (1) and cyclo(l-Pro-l-Ile) (2)] and one N-phenethylacetamide (3). Cyclo(l-Pro-l-Leu) (1) and N-phenethylactamide (3) inhibited the TGF-β/Smad pathway and suppressed the metastasis of A549 cells by affecting TGF-β-induced EMT. However, cyclo(l-Pro-l-Ile) (2) downregulated mesenchymal factors via a non-Smad-mediated signaling pathway.

Keywords

• <i>Aquimarina</i> sp.
• diketopiperazine
• N-phenethylacetamide
• epithelial-mesenchymal transition (EMT)
• A549 cells