Chemical Investigation of Diketopiperazines and N-Phenethylacetamide Isolated from Aquimarina sp. MC085 and Their Effect on TGF-?-Induced Epithelial–Mesenchymal Transition

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