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Activities of quinoxaline, nitroquinoxaline and [1,2,4]triazolo[4,3-a]quinoxaline analogs of MMV007204 against; Schistosoma mansoni

Debbert, S. L. and Hintz, M. J. and Bell, C. J. and Earl, K. R. and Forsythe, G. E. and Häberli, C. and Keiser, J.. (2021) Activities of quinoxaline, nitroquinoxaline and [1,2,4]triazolo[4,3-a]quinoxaline analogs of MMV007204 against; Schistosoma mansoni. Antimicrobial agents and chemotherapy, 65 (3). e01370-20.

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Official URL: https://edoc.unibas.ch/89050/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Helminth Drug Development (Keiser)
UniBasel Contributors:Häberli, Cécile and Keiser, Jennifer
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:0066-4804
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Dec 2022 09:33
Deposited On:20 Dec 2022 09:33

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