In vitro Testing of KG Drug Derivatives Against Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular parasite that causes a potentially lethal infection called toxoplasmosis in immunocompromised human individuals, such as pregnant women and individuals with immune deficiencies. To date, there are a handful of therapeutic drugs such as pyrimethamine and sulfadiazine that are able to combat acute infection, but not without deleterious effects to the host. The development of a drug that has both increased efficacy and safety over currently existing therapies would be extremely valuable in clinical treatment of toxoplasmosis. Previous work in our lab has identified a potentially promising class of drugs, known as KG drugs. Preliminary testing of KG drugs in vivo indicated partial protection against T.gondii infection. The purpose of this research was to test analogues of KG drugs in vitro against T.gondii infection to identify compounds with promising potential for further testing in animal subjects. KG analogues were generated in collaboration with the College of Pharmacy at the University of Nebraska Medical Center. Our results identified 10 KG derivatives that were effective against T.gondii infection at concentrations close to or lower than pyrimethamine, the current standard for clinical treatment. In addition, these drugs showed little to no toxicity to host cells in vitro. These results suggest the potential of KG drug derivatives as viable anti-Toxoplasma therapeutic options