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Investigating The Antimalarial Action Of 1,2,4-Trioxolanes With Fluorescent Chemical Probes, Carmony L. Hartwig, Erica M. W. Lauterwasser, Sumit S. Mahajan, Jonathan M. Hoke, Roland Cooper, Adam R. Renslo
Investigating The Antimalarial Action Of 1,2,4-Trioxolanes With Fluorescent Chemical Probes, Carmony L. Hartwig, Erica M. W. Lauterwasser, Sumit S. Mahajan, Jonathan M. Hoke, Roland Cooper, Adam R. Renslo
Roland A. Cooper
The 1,2,4-trioxolanes are a new class of synthetic peroxidic antimalarials currently in human clinical trials. The well known reactivity of the 1,2,4-trioxolane ring towards inorganic ferrous iron and ferrous iron heme is proposed to play a role in the antimalarial action of this class of compounds. We have designed structurally relevant fluorescent chemical probes to study the sub-cellular localization of 1,2,4-trioxolanes in cultured Plasmodium falciparum parasites. Microscopy experiments revealed that a probe fluorescently labeled on the adamantane ring accumulated specifically in digestive vacuole-associated neutral lipid bodies within the parasite while an isosteric, but non-peroxidic congener did not. Probes fluorescently labeled …