Author ORCID Identifier

0000-0002-9662-2220

Month/Year of Graduation

5-2023

Degree Name

Bachelor of Science (B.S.)

Department

Biology

First Advisor

Dr. Paul H. Davis

Abstract

Toxoplasma gondii, the causative agent of toxoplasmosis, is an intracellular apicomplexan parasite. Toxoplasmosis is often asymptomatic, though, it can be debilitating or fatal to immunocompromised individuals and fetuses, being one of the leading causes of fetal mortality and birth defects. Toxoplasmosis is treated with a synergistic combination of drugs pyrimethamine and sulfadiazine; however, these drugs are only effective against the acute stage of infection, and the pyrimethamine is relatively cytotoxic, damaging bone marrow and causing noxious side effects. Due to these limitations, a safer alternative that targets the chronic stage of infection is needed. In this study, we tested compounds of two putative anti-malarial chemotypes against RH T. gondii (Type I strain) in vitro. Inhibition was determined by calculating the half-maximal inhibition concentration (IC50) from dose-response curves of the RH strain transgenically expressing dimerized Tomato (dTom) using relative fluorescent values (RFU) as a readout of viability. Four of the compounds (MJ17IC50 = 0.09 μM; MJ52IC50 = 0.08 μM; MJ07IC50 = 0.26 μM; and MJ27IC50 = 0.11 μM) were more potent than pyrimethamine (IC50 = 0.69 μM) in vitro and were less cytotoxic as well. Future directions include testing these compounds against tachyzoites and bradyzoites of the Type II strain in vitro and ultimately in vivo.

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