Acridones Are Highly Potent Inhibitors of Tachyzoites.
This work was supported by Career Development Award BX002440 and VA Merit Review Award BX004522 to J.S.D. from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development and NIH/NIAID Award 1R01AI093784 and DOD/PRMRP Award PR160693/W81XWH-17-2-0041 to J.X.K. The National Science Foundation is acknowledged for support of the BioAnalytical Mass Spectrometry Facility at Portland State University (MRI 1828573).
ACS Infectious Diseases
Acridone derivatives, which have been shown to have and activity against spp, inhibit proliferation at picomolar concentrations. Using enzymatic assays, we show that acridones inhibit both cytochrome and dihydroorotate dehydrogenase and identify acridones that bind preferentially to the Q site of cytochrome . We identify acridones that have efficacy in a murine model of systemic toxoplasmosis. Acridones have potent activity against and represent a promising new class of preclinical compounds.
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Alday, P. H., McConnell, E. V., Boitz Zarella, J. M., Dodean, R. A., Kancharla, P., Kelly, J. X., & Doggett, J. S. (2021). Acridones Are Highly Potent Inhibitors of Toxoplasma gondii Tachyzoites. ACS Infectious Diseases, acsinfecdis.1c00016. https://doi.org/10.1021/acsinfecdis.1c00016