Highly N -Methylated Peptides from the Antarctic Sponge Inflatella coelosphaeroides Are Active against Plasmodium falciparum .

Malaria, caused by the parasite Plasmodium falciparum , continues to threaten much of the world's population, and there is a pressing need for expanding treatment options. Natural products have been a vital source of such drugs, and here we report seven new highly N -methylated linear peptides, friomaramide B ( 2 ) and shagamides A-F ( 3 - 8 ) from the marine sponge Inflatella coelosphaeroides , collected in Antarctic waters, which demonstrate activity against three strains of blood-stage P. falciparum. The planar structures of these metabolites were solved by interpreting NMR data, as well as HRESIMS/MS fragmentation patterns, while Marfey's analysis was used to establish the configurations of the amino acids. Reisolation of the previously reported compound friomaramide A ( 1 ) allowed us to revise its structure. The panel of isolated compounds allowed establishing structure/activity relationships and provided information for future structure optimization for this class of P. falciparum inhibitory metabolites.