The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity

A library of enrichedmarine natural product fractions was screened for their antiplasmodial activity using a SYBR green I fluorescence-based assay. Fractions derived from a sponge of the genus Spongosorites exhibited potent inhibition of Plasmodium falciparum growth. This genus of sponge has been reported to contain the nortopsentin and topsentin class of bis-indole imida-zole alkaloids. This is the first report of nortopsentin A inhibiting parasite growth at the trophozoite stage at submicromolar 50 % inhibitory concentrations (IC50). Over 300 million clinical cases of malaria occur annually, re-sulting in more than 1 million deaths (1). Unfortunately, because of the prevalence of drug-resistant malaria parasite strains, existing drugs are increasingly losing their efficacy. There-fore, there is an urgent need to identify new drug leads to reduce the globalmalaria burden.Marine biological diversity provides an excellent opportunity to identify novel drug leads from secondary metabolites of marine organisms. Although research aiming to discover novel marine-derived antiplasmodial agents is relatively recent, over 60 active compounds have been reported to date (2). One of the more important leads is manzamine A, a structurall