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To address this problem, we prepared a set of dual\u2010acting tetraoxane\u2010based hybrid molecules designed to deliver a falcipain\u20102 (FP\u20102) inhibitor upon activation by iron(II) in the parasite digestive vacuole. These hybrids are active in the low nanomolar range against chloroquine\u2010sensitive and chloroquine\u2010resistant <jats:italic>P.\u2005falciparum<\/jats:italic> strains. We also demonstrate that in the presence of FeBr<jats:sub>2<\/jats:sub> or within infected red blood cells, these molecules fragment to release falcipain inhibitors with nanomolar protease inhibitory activity. Molecular docking studies were performed to better understand the molecular interactions established between the tetraoxane\u2010based hybrids and the cysteine protease binding pocket residues. 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