Antimalarial Peptide and Polyketide Natural Products from the Fijian Marine Cyanobacterium .

A new cyclic peptide, kakeromamide B (), and previously described cytotoxic cyanobacterial natural products ulongamide A (), lyngbyabellin A (), 18-lyngbyaloside C (), and lyngbyaloside () were identified from an antimalarial extract of the Fijian marine cyanobacterium . Compounds and exhibited moderate activity against blood-stages with EC values of 0.89 and 0.99 µM, respectively, whereas was more potent with an EC value of 0.15 nM, respectively. Compounds , , and displayed moderate liver-stage antimalarial activity against liver schizonts with EC values of 1.1, 0.71, and 0.45 µM, respectively. The threading-based computational method FINDSITE predicted the binding of and to potentially druggable proteins of , prompting formulation of hypotheses about possible mechanisms of action. Kakeromamide B () was predicted to bind to several actin-like proteins and a sortilin protein suggesting possible interference with parasite invasion of host cells. When 1 was tested in a mammalian actin polymerization assay, it stimulated actin polymerization in a dose-dependent manner, suggesting that 1 does, in fact, interact with actin.