and Antischistosomal Activity Profiling and Pharmacokinetics of Ozonide Carboxylic Acids.

Praziquantel, the only drug in clinical use for the treatment and control of schistosomiasis, is inactive against developing infections. Ozonides are synthetic peroxide derivatives inspired by the naturally occurring artemisinin and show particularly promising activity against juvenile schistosomes. We conducted an in-depth characterization of the and antischistosomal activity and pharmacokinetics of lead ozonide carboxylic acid OZ418 and four of its active analogs. , the ozonides featured rapid and consistent activity against schistosomula and adult schistosomes at double-digit micromolar EC values. Potency did not vary considerably between The zwitterionic OZ740 and OZ772 were more active compared to their non-amphoteric carboxylic acids OZ418 and OZ748, despite their much lower systemic plasma exposure (AUC). The most active compound was ethyl ester OZ780, which was rapidly transformed to its parent zwitterion OZ740 and achieved ED values of 35 ± 2.4 and 29 ± 2.4 mg/kg against adult and juvenile , respectively. Ozonide carboxylic acids represent promising candidates for further optimization and development due to their good efficacy against both life stages together with their broad activity range against all relevant parasite species.