Future antimalarials from ? A rationale for natural product mining against drug-refractory stages.

Covering: up to 2023Infusions of the plants and are gaining broad popularity to prevent or treat malaria. There is an urgent need to address this controversial public health question by providing solid scientific evidence in relation to these uses. Infusions of either species were shown to inhibit the asexual blood stages, the liver stages including the hypnozoites, but also the sexual stages, the gametocytes, of parasites. Elimination of hypnozoites and sterilization of mature gametocytes remain pivotal elements of the radical cure of , and the blockage of and transmission, respectively. Drugs active against these stages are restricted to the 8-aminoquinolines primaquine and tafenoquine, a paucity worsened by their double dependence on the host genetic to elicit clinical activity without severe toxicity. Besides artemisinin, these spp. contain many natural products effective against asexual blood stages, but their activity against hypnozoites and gametocytes was never investigated. In the context of important therapeutic issues, we provide a review addressing (i) the role of artemisinin in the bioactivity of these infusions against specific parasite stages, , alone or in association with other phytochemicals; (ii) the mechanisms of action and biological targets in of 60 infusion-specific phytochemicals, with an emphasis on drug-refractory parasite stages (, hypnozoites and gametocytes). Our objective is to guide the strategic prospecting of antiplasmodial natural products from these spp., paving the way toward novel antimalarial "hit" compounds either naturally occurring or -inspired.