New Theonellapeptolides from Indonesian Marine Sponge Theonella swinhoei as Anti-Austerity Agents.

We reported three new members of the theonellapeptolide family from theonellapeptolide II series, namely theonellapeptolides IIb ( 1 ), IIa ( 2 ), IIc ( 3 ), and three known members-IId ( 4 ), IIe ( 5 ), and Id ( 6 )-from Kodingarengan marine sponge Theonella swinhoei collected in Makassar, Indonesia. The structures of tridecadepsipeptides 1 - 3 , including the absolute configurations of their amino acids, were determined by the integrated NMR and tandem MS analyses followed by Marfey's analysis. To the best of our knowledge, 1 and 2 are the first theonellapeptolide-type compounds to have a valine residue with D configuration at residue position 6. The isolated theonellapeptolide-type compounds 1 - 6 showed selective cytotoxic activity against human pancreatic MIA PaCa-2 cancer cells in a nutrient-deprived medium. Among them, the most potent preferential cytotoxicity was observed in new theonellapeptolide IIc ( 3 ) and known IId ( 4 ), IIe ( 5 ), and Id ( 6 ).