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Benoit-Vical, F. et al.

Benoit-Vical, Lelièvre, Berry, Deymier, Dechy-Cabaret, Cazelles, Loup, Robert, Magnaval, Meunier,

Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes.

Malaria is the third most significant cause of infectious disease in the world. The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to classical drugs. Trioxaquines are synthetic hybrid molecules containing a trioxane motif (which is responsible for the antimalarial activity of artemisinin) linked to an aminoquinoline entity (which is responsible for the antiplasmodial properties of chloroquine). These trioxaquines are highly potent against young erythrocytic stages of Plasmodium falciparum and exhibit efficient activity in vitro against chloroquine-sensitive and -resistant strains of P. falciparum (50% inhibitory concentration, 4 to 32 nM) and are also active in vivo against P. vinckei petteri and P. yoelii nigeriensis in suppressive and curative murine tests. The trioxaquine DU1302 is one of these promising antimalarial agents. The present study confirms the absence of toxicity of this drug on cell lines and in a mice model. Moreover, DU1302 exhibits potent activity against gametocytes, the form transmitted by mosquitoes, as killing of the gametocytes is essential to limit the spread of malaria. The ease of chemical synthesis of this trioxaquine prototype should be considered an additional advantage and would make these drugs affordable without perturbations of the drug supply.[1]

References

Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Benoit-Vical, F., Lelièvre, J., Berry, A., Deymier, C., Dechy-Cabaret, O., Cazelles, J., Loup, C., Robert, A., Magnaval, J.F., Meunier, B. Antimicrob. Agents Chemother. (2007) [Pubmed]

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