N. Lopes

Antimalarial Effect of 3-Methoxy-1,2-Dioxetanes on the Erythrocytic Cycle of Plasmodium falciparum.

The antimalarial activity of peroxides most likely originates from their interaction with iron(II) species located inside the malaria parasite, which forms destructive radical species through a Fenton‐like mechanism. This article reports the first evaluation of the in vitro antimalarial activity of three peroxides of the class 1,2‐dioxetanes against Plasmodium falciparum; the results reveal that the studied 3‐methoxy‐1,2‐dioxetanes display significant antimalarial activity, at a similar level as artemisinin and also that their reactivity toward iron(II) correlate linearly with their antimalarial activity.

Kinetic parameters for the reaction of 1,2,4‐trioxolanes and artemisinin with iron(II): New evidence for the source of antimalarial activity

The Fenton‐like reductive cleavage of antimalarial peroxides like artemisinin by iron(II) species is a chemical reaction whose mechanistic pathway has not been yet fully understood; it is, however, known that there is considerable production of radical species centered at both the oxygen and carbon, which are important to the therapeutical effects of those compounds. This article reports kinetic data for the reaction of artemisinin and two model 1,2,4‐trioxolanes with iron(II) species and also a mechanistic interpretation of this reductive cleavage from transition state thermodynamics. The suggestion of the presence of an enhancing specific factor inside the plasmodium is made.