Activities of Quinoxaline, Nitroquinoxaline, and [1,2,4]Triazolo[4,3-a]quinoxaline Analogs of MMV007204 against Schistosoma mansoni.

The reliance on one drug, praziquantel, to treat the parasitic disease schistosomiasis in millions of people a year shows the need to further develop a pipeline of new drugs to treat this disease. Recently, an antimalarial quinoxaline derivative (MMV007204) from the Medicines for Malaria Venture (MMV) Malaria Box demonstrated promise against In this study, 47 synthesized compounds containing quinoxaline moieties were first assayed against the larval stage of this parasite, newly transformed schistosomula (NTS); of these, 16 killed over 70% NTS at 10 µM. Further testing against NTS and adult yielded three compounds with 50% inhibitory concentrations (ICs) of ≤0.31 µM against adult and selectivity indices of ≥8.9. Administration of these compounds as a single oral dose of 400 mg/kg of body weight to infected mice yielded only moderate worm burden reduction (WBR) (9.3% to 46.3%). The discrepancy between these compounds' good activities and their poor activities indicates that optimization of their pharmacokinetic properties may yield compounds with greater bioavailabilities and better antischistosomiasis activities .