Antiplasmodial activity of tambjamines, dihydro-β-agarofurans and pyrroloazepines derived from Australian plant and marine species

Malaria is a significant cause of morbidity and mortality, with 263 million cases and 597,000 deaths estimated in 2023. While effective drug combinations are available to prevent and treat malaria, Plasmodium parasite drug resistance is compromising all current options. This situation means that new drugs that act on novel Plasmodium drug targets are needed. Natural products, including artemisinin, derived from Artemisia annua, and its derivatives, have been an important source of antimalarials. In this study we investigated a panel of 43 compounds from the NatureBank natural product library for in vitro activity against asexual stage P. falciparum parasites. Four compounds isolated from Australian plant and marine samples were identified with novel antiplasmodial activity - tambjamine F (IC₅₀ 1.06 μM) and tambjamine C (IC₅₀ 3.40 μM) from the marine ascidian Sigillina signifera, bilocularin B (IC₅₀ 2.18 μM) from the rainforest plant Maytenus bilocularis and hymenialdisine (IC₅₀ 2.90 μM) from the marine sponge Acanthella costata.