Acridones Are Highly Potent Inhibitors of Tachyzoites

Authors

P. Holland Alday, Portland VA Medical Center
Erin V. McConnell, Portland VA Medical Center
Jan M. Boitz Zarella, Portland VA Medical Center
Rozalia A. Dodean, Portland VA Medical Center
Papireddy Kancharla, Portland State UnivesityFollow
Jane X. Kelly, Portland State UniversityFollow
J. Stone Doggett, Portland State University

Sponsor

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).

Published In

ACS Infectious Diseases

Document Type

Citation

Publication Date

3-16-2021

Abstract

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.

Rights

Copyright © 2021 by the American Chemical Society.

Locate the Document

https://doi.org/10.1021/acsinfecdis.1c00016

DOI

10.1021/acsinfecdis.1c00016

Persistent Identifier

https://archives.pdx.edu/ds/psu/35080

Citation Details

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