Abstract by Garrett Parker
Chemistry and Biochemistry
Glucose Uptake Inhibitors of Trypanosoma brucei
Trypanosoma brucei (T. brucei) is a single-celled eukaryotic parasite responsible for Human African Trypanosomiasis (HAT). HAT is fatal unless treated and several current treatments are highly toxic. T. brucei relies exclusively on glycolysis for ATP so our lab screened 25,000 small molecules to identify glucose uptake inhibitors as possible starting points for new HAT treatments. Several compounds effectively inhibited glucose uptake in the parasite. To determine the potential host toxicity of these compounds, a live/dead resazurin assay was performed in HEK293T cells. Many of the compounds were found to exhibit no toxicity even at 50 µM. Interestingly, compound specificity for parasites was high as compounds also had very limited activity against the human glucose transporter hGLUT1. An update will also be provided on our efforts to develop NIR metabolite sensors to allow parasite metabolic monitoring in mouse models of parasite infection. In addition to testing compound efficacy in animals, this NIR sensor could be used to study how the parasite alters its metabolism in different host tissues, such as a recently identified phenotype in adipose tissue.