Acridones Are Highly Potent Inhibitors of Toxoplasma gondii Tachyzoites

被引：7

作者：

Alday, P. Holland ^{[1
]}

McConnell, Erin, V ^{[1
]}

Zarella, Jan M. Boitz ^{[1
]}

Dodean, Rozalia A. ^{[1
]}

Kancharla, Papireddy ^{[2
]}

Kelly, Jane X. ^{[1
,2
]}

Doggett, J. Stone ^{[1
]}

机构：

[1] Portland VA Med Ctr, Portland, OR 97239 USA

[2] Portland State Univ, Dept Chem, Portland, OR 97201 USA

来源：

ACS INFECTIOUS DISEASES | 2021年 / 7卷 / 07期

基金：

美国国家科学基金会;

关键词：

toxoplasma; acridone; cytochrome bc(1); dihydroorotate dehydrogenase; drug discovery; DIHYDROOROTATE DEHYDROGENASE; PROTECTIVE IMMUNITY; STRAINS; PARASITE;

D O I：

10.1021/acsinfecdis.1c00016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Acridone derivatives, which have been shown to have in vitro and in vivo activity against Plasmodium spp, inhibit Toxoplasma gondii proliferation at picomolar concentrations. Using enzymatic assays, we show that acridones inhibit both T. gondii cytochrome bc(1) and dihydroorotate dehydrogenase and identify acridones that bind preferentially to the Q site of cytochrome bc(1). We identify acridones that have efficacy in a murine model of systemic toxoplasmosis. Acridones have potent activity against T. gondii and represent a promising new class of preclinical compounds.

引用

页码：1877 / 1884

页数：8

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