SYK INHIBITORS AS NEW ANTIMALARIAL DRUGS

Resistance to antimalarial drugs has spread rapidly over the past few decades, therefore to overcome it, WHO recommends Artemisinin based combination therapies (ACTs) for the treatment against Plasmodium falciparum malaria. Although these treatments are effective in many parts of the world, there is serious concern that malaria parasites are once again developing widespread resistance to this vital treatment. To date, artemisinin resistance has been confirmed in 5 countries of the Greater Mekong subregion. The development of resistance has highlighted the need for the search of novel antimalarial molecules. Recently, it was demonstrated that Syk inhibitors represent a new class of antimalarial drugs that suppress merozoite egress by inhibiting a host target that cannot be mutated by the parasite to develop drug resistance. Our purpose was to evaluate the antiplasmodial activity of different Syk inhibitors using in vitro approach and to have more information on the mechanisms responsible for the protein-ligand recognition. A detailed understanding of Syk Kinase inhibition is the central focus, in order to understanding biology at the molecular level, with the future perspectives of discovering new class of drugs to obtain the highest efficacy of inhibition in infected RBCs.