Malaria, caused by the parasite Plasmodium falciparum, continues to threaten much of the world population and there is a pressing need for expanding treatment options. Recently, it has been observed that artemisinin combination therapy, which has been the gold standard for malaria treatment, is now starting to fail in some African countries. Thus better treatments are required, marine sponges leading to at least 259 unique metabolites have demonstrated anti-Plasmodium falciparum activity. The researcher previously investigated sponge Inflatella coelosphaeroides for malaria therapeutics and spectroscopic analysis. In this technology, the researchers focus on the un-analyzed Inflatella coelosphaeroides extract fractions, along with the methanolic extract of a previously unexplored specimen, this showed many signals indicative of other N-methylated peptides. These peptides are unusual in their high level of N-methylation and unusual N-terminal substitution, and one of them has an unusual tryptenamine C-terminal. They display potent activity against Plasmodium falciparum, the causative parasite of malaria, including one drug resistant strain.
The image illustrates mid-polarity fractions extracted from the sponge Inflatella and the contained metabolites bearing multiple N-methyl groups, reminiscent of friomaramide (friomaramide A) (1) and the purified seven new highly methylated peptides, including friomaramide B (2) and six peptides without the characteristic tryptenamine function found on the friomaramides, shagamides A-F (3-8).