The parasite Toxoplasma gondii infects up to one-third of the human population, experts say. Sometimes transmitted to humans from infected cat feces or litter, the protozoan can cause severe and even deadly illnesses in immunocompromised people and fetuses. Now, researchers reporting in ACS Infectious Diseases have discovered that common herbicides and some of their derivatives can kill the parasite when it infects human cells in a petri dish, without harming the cells themselves.
T. gondii infection usually occurs from eating undercooked contaminated meat, exposure to infected cat feces or mother-to-child transmission during pregnancy. The parasite causes mild or no symptoms in most people, but it can cause severe illnesses in immunocompromised people and birth defects in the fetuses of pregnant women. Current therapies have limitations, such as strong side effects and an inability to cross the placenta to treat the fetus. They also don’t work well for chronic infections. Recently, scientists discovered that T. gondii expresses an enzyme (protoporphyrinogen oxidase, or PPO) that more closely resembles the plant version of the enzyme than the mammalian one. Plant PPO, which helps make an essential compound called heme, is the target of some common herbicides, including oxadiazon. Kerrick Rees, Zhicheng Dou and Daniel Whitehead wondered if these herbicides or their derivatives could kill not only weeds, but also T. gondii — without harming human cells.
The researchers screened several herbicides for the ability to kill T. gondii that had infected human cells in a dish, finding that oxadiazon and a related compound, oxadiargyl, were the most effective. Then, they synthesized 18 derivatives of oxadiargyl that had different chemical groups at a certain region of the molecule, identifying some that were even more potent than the parent compound. In other experiments, the researchers confirmed that the herbicide derivatives work primarily by inhibiting PPO. Importantly, the compounds didn’t harm human cells that hosted the parasites. Next, the researchers plan to test the most potent molecules in an animal model of T. gondii infection.
The authors acknowledge funding from the National Institutes of Health.
The paper’s abstract will be available on April 6 at 8 a.m. Eastern time here: http://pubs.acs.org/doi/abs/10.1021/acsinfecdis.2c00020
The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.
To automatically receive news releases from the American Chemical Society, contact [email protected]
Follow us: Twitter | Facebook | LinkedIn | Instagram
ACS Infectious Diseases
Oxadiazon derivatives elicit potent intracellular growth inhibition against toxoplasma gondii by disrupting heme biosynthesis
Article Publication Date