Overview of natural antiplasmodials from the last decade to inspire medicinal chemistry.

Background Despite the major advances in the fight against this parasitic disease, malaria remains a major cause of concerns in 2020. This infection, mainly due to Plasmodium falciparum, causes every year more than 200 million of cases and hundreds of thousands of deaths in developing regions, mostly in Africa. The last statistics show an increase of cases for the third consecutive year, from 211 million in 2015, it has reached 229 million in 2019. This trend could be partially explained by the appearance of resistances to all the used antimalarials, even to artemisinin. Thus, the design of new anti-Plasmodium compounds is an urgent need. For thousands of years, nature has offered to humans the medicines to cure their diseases or the inspiration for development of new active principles. It seems then logical to explore the natural sources to find new molecules to treat this parasitosis. Method Therefore, this review reports and analyzes the extracts (plants, bacteria, sponges, fungi) and the corresponding isolated compounds showing antiplasmodial properties between 2013 and 2019. Results & conclusion Nature remains a major source of active compounds. Indeed, 648 molecules from various origins, mostly plants, have been reported for their inhibitory effect on Plasmodium falciparum. Among them, 188 scaffolds were defined as highly active with IC50 ≤ 5 µM and have been reported here in details. Moreover, the most active compounds showed a large variety of structures: flavonoids, triterpenes, alkaloids... Therefore, these compounds could be an interesting source of inspiration for medicinal chemists. May-be several of these molecules should become the next leads for malaria treatment.