Nitrogen-containing bisphosphonates, drugs used to treat bone resorption diseases, also have activity against a broad range of protists, including blood-stage Plasmodium spp. Here, we show that new-generation "lipophilic" bisphosphonates designed as anticancer agents that block protein prenylation also have potent activity against Plasmodium liver stages, with a high (>100) therapeutic index.
Fatty acids are essential components of membranes, and are also involved in cell signalling. Plasmodium, the parasite that causes malaria, scavenges fatty acids from its hosts. However, Plasmodium also possesses enzymes for a prokaryotic-like de novo fatty acid synthesis pathway, which resides in the apicoplast. Recent research has demonstrated that Plasmodium parasites depend on de novo fatty acid synthesis only for liver-stage development.