Antimalarial Bicyclic Peroxides Belonging to the G-Factor Family: Mechanistic Aspects of their Formation and Iron (II) Induced Reduction
Artemisinin and its derivatives are peroxide-containing compounds targeting P. falciparum. We review here
structural analogues of bicyclic peroxides belonging to the G factors family presenting antimalarial properties. They were
synthesised under Mannich type conditions, followed by an autoxidation step resulting exclusively in the peroxide. As the
electron transfer from haem or free iron to the peroxide is the first step in the mode of action of artemisinin-like compounds,
the redox properties of some endoperoxides were studied by electrochemistry allowing the evaluation of the reduction
standard potentials. The Fe(II) induced reduction was also investigated and the reactivity of the C-centered radical
intermediate formed was linked to the antimalarial activity. These bicyclic peroxides both with various hybrid molecules
containing the endoperoxide framework were evaluated in vitro against Plasmodium falciparum. They exhibited moderate
to good activities.
Keywords: C-centered radical, cyclic peroxide, hybrid molecules, malaria.
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