Modulation of the Host-Parasite Redox Metabolism to Potentiate Antimalarial Drug Efficiency

Artemisinin-based combination therapy (ACT) is nowadays the most effective treatment for P. falciparum malaria: artemisinin is the most active drug able to rapidly kill all erythrocyte stages of the malaria parasite. However, due to its short half-life, it requires the association with other long-acting drugs. Even if the exact mechanism of action of most antimalarial drugs is still unknown, many of these compounds are able to interact directly or indirectly with the redox metabolism of the parasite and/or the host, enhancing the effectiveness of the antimalarial therapy. This review focuses on many natural compounds, isolated mainly from plants, and used as traditional antimalarial treatments, known to possess a potent antimalarial activity (IC50 lower than 1 ug/mL). These compounds belong to some specific chemical family, mainly alkaloids, terpenoids, quassinoids, limonoids, and polyphenols, sharing some common chemical features. These natural molecules could offer new possibilities of combination therapies development as antimalarials when associated with artemisinin.