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

Journal of Natural Products
2022.0

Abstract

Malaria, caused by the parasite <i>Plasmodium falciparum</i>, 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 <i>N</i>-methylated linear peptides, friomaramide B (<b>2</b>) and shagamides A-F (<b>3</b>-<b>8</b>) from the marine sponge <i>Inflatella coelosphaeroides</i>, collected in Antarctic waters, which demonstrate activity against three strains of blood-stage <i>P. falciparum.</i> 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 (<b>1</b>) 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 <i>P. falciparum</i> inhibitory metabolites.

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