Event Title

Utilizing Novel Scaffolds to Target Cytochrome-B of Toxoplasma gondii Tachyzoites

Session Number

P03

Advisor(s)

Kamal El-Bissati, University of Chicago
Farida Esaa, University of Chicago
Rima McLeod, University of Chicago
Ying Zhou, University of Chicag

Location

B-206 Lecture Hall

Start Date

28-4-2016 8:50 AM

End Date

28-4-2016 9:15 AM

Disciplines

Medicine and Health Sciences

Abstract

Toxoplasma gondii, an apicomplexan parasite affecting one third of the world’s population, causes the disease known as toxoplasmosis. Atovaquone is a current treatment against T.gondii which can partially reduce the number of bradyzoites. However, atovaquone-resistant mutants are rapidly selected during treatment with atovaquone. Atovaquone and related compounds have been developed against cytochrome b, a target within complex III of the parasite’s electron transport chain, hypothesized to be a key component of adenosine triphosphate production within the parasite. A parasite assay determined compounds’ effects upon T. gondii tachyzoites. Human foreskin fibroblasts (HFF) in 96-well plates were utilized as in vitro models. T. gondii tachyzoites invaded HFFs before compound concentrations of 0.03 micromolar (uM) to 10uM were added. A toxicity assay determined the effect of the compound upon HFFs. Varying concentrations of each compound were added to HFFs before WST-1 was added to quantify mitochondrial activity of remaining living HFFs. JAG021 and JAG050 led to significant decreases in parasites at compound concentrations from 0.125uM to 10uM. Additionally, all compounds had minimal levels of toxicity from 1uM- 10uM with exception of HFF toxicity at 15uM. Further studies will be conducted to determine the effects of the compounds within in vivo models to develop the compounds into medicines.


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Apr 28th, 8:50 AM Apr 28th, 9:15 AM

Utilizing Novel Scaffolds to Target Cytochrome-B of Toxoplasma gondii Tachyzoites

B-206 Lecture Hall

Toxoplasma gondii, an apicomplexan parasite affecting one third of the world’s population, causes the disease known as toxoplasmosis. Atovaquone is a current treatment against T.gondii which can partially reduce the number of bradyzoites. However, atovaquone-resistant mutants are rapidly selected during treatment with atovaquone. Atovaquone and related compounds have been developed against cytochrome b, a target within complex III of the parasite’s electron transport chain, hypothesized to be a key component of adenosine triphosphate production within the parasite. A parasite assay determined compounds’ effects upon T. gondii tachyzoites. Human foreskin fibroblasts (HFF) in 96-well plates were utilized as in vitro models. T. gondii tachyzoites invaded HFFs before compound concentrations of 0.03 micromolar (uM) to 10uM were added. A toxicity assay determined the effect of the compound upon HFFs. Varying concentrations of each compound were added to HFFs before WST-1 was added to quantify mitochondrial activity of remaining living HFFs. JAG021 and JAG050 led to significant decreases in parasites at compound concentrations from 0.125uM to 10uM. Additionally, all compounds had minimal levels of toxicity from 1uM- 10uM with exception of HFF toxicity at 15uM. Further studies will be conducted to determine the effects of the compounds within in vivo models to develop the compounds into medicines.