Graduation Year

2016

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Chemistry

Major Professor

James W. Leahy, Ph.D.

Committee Member

Roman Manetsch, Ph.D.

Committee Member

Bill Baker, Ph.D.

Committee Member

Michael White, Ph.D.

Committee Member

Juan Del Valle, Ph.D.

Keywords

malaria, Plasmodium, toxoplasmosis, Toxoplasma gondii, kinase inhibitors, anti-malarials, Shield-1, SB-505124

Abstract

Toxoplasmosis is an opportunistic disease caused by the protozoan parasite Toxoplasma gondii. The parasite is usually staved off by a healthy immune system and remains dormant in the body. In immunocompromised patients, the parasite can become active and spread throughout the body causing symptoms such as encephalitis, cognitive disorders, seizures, and death. Combination drug therapy is the usual treatment for toxoplasmosis; however, patients suffer from problems of intolerance, allergic reactions, and cytotoxicity. In an effort to identify new drug targets for toxoplasmosis, a series of compounds have been synthesized that can be used as tools to probe the unique pathways used by T. gondii to survive in the human host. One class of these compounds is pyridinyl imidazoles, which have been shown to be active against T. gondii MAP kinases. To set up a protein pull down assay, a biotinylated linker was synthesized. We have also synthesized a compound that’s being used to study the pathways involved in the most active and proliferative form of T. gondii.

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