Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
Activities of quinoxaline, nitroquinoxaline and [1,2,4]triazolo[4,3-a]quinoxaline analogs of MMV007204 against; Schistosoma mansoni
Journal
Antimicrobial agents and chemotherapy
Volume
65
Number
3
Pages / Article-Number
e01370-20
Abstract
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 Schistosoma mansoni 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 muM. Further testing against NTS and adult S. mansoni yielded three compounds with 50% inhibitory concentrations (IC50s) of /= 8.9. Administration of these compounds as a single oral dose of 400 mg/kg of body weight to S. mansoni -infected mice yielded only moderate worm burden reduction (WBR) (9.3% - 46.3%). The discrepancy between these compounds' good in vitro activities and their poor in vivo activities indicates that optimization of their pharmacokinetic properties may yield compounds with greater bioavailabilities and better antischistosomiasis activities in vivo.
