salinipostin A

Salinipostin A (Sal A) is a potent, marine-derived bicyclic phosphotriester natural product isolated from the marine actinomycete genus *Salinispora* (specifically *Salinispora tropica*). It exhibits potent antimalarial activity against asexual blood-stage *Plasmodium falciparum* parasites, particularly during schizogony, with a low propensity for generating resistance. Salinipostin A acts as a covalent inhibitor of multiple essential parasite serine hydrolases involved in lipid metabolism, including *Plasmodium falciparum* monoacylglycerol lipase-like protein (PfMAGLLP, PF3D7_1038900), *Plasmodium falciparum* prodrug activation and resistance esterase (PfPARE, PF3D7_0709700), and PfXL2. It also inhibits human depalmitoylases APT1 and APT2, as well as acetylcholinesterase. In vitro resistance selections have identified mutations in the mitochondrial PRELI domain-containing protein (PfPRELI, PF3D7_1324400) as a key resistance node.

Other names

Sal A