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Graduation Term

2017

Degree Name

Master of Science (MS)

Department

Department of Chemistry

Committee Chair

Craig C. McLauchlan

Abstract

Leishmania is a genus of single cell parasitic organisms that are the cause of the leishmaniasis, a disease that can manifest itself as skin disorders or internal infections. These organisms are commonly found in the arid regions of the Middle East, as well as areas in and surrounding Central America and parts of South America, as well as India. Current medical treatments for leishmaniasis, including sodium stibogluconate (an antimony containing drug) and amphotericin B (an antifungal drug), are expensive and have undesirable side effects such as nausea, abdominal pain, and anorexia, leading to large numbers of the infected populations remaining untreated. If untreated, leishmaniasis can lead to permanent disfigurement, co-infections, or even death. For these reasons, newer and safer therapeutic drugs for leishmaniasis are desired. Using the species Leishmania tarentolae as a model system, previously synthesized vanadium complexes were tested for their anti-leishmanial properties, thus potential therapies. Two of these complexes have previously been tested in phase II clinical trials for the treatment of diabetes mellitus owing to their ability to inhibit tyrosine phosphatase, allowing for better glucose regulation in diabetic persons. Incubation of the L. tarentolae with vanadium complexes and testing the viability of cells will help determine the potential for a new class of therapeutic drugs against leishmaniasis, which affects fifteen to twenty million people worldwide. Our latest results include the synthesis and characterization of nine vanadium coordination complexes. Incubation of synthesized vanadium complexes with L. tarentolae indicated that vanadium(IV) complexes exhibit greater reduction in cell viability than vanadium(V) complexes. Michaelis-Menten kinetics using wheat germ acid phosphatase incubated with di(maltolato)oxovanadium(IV) indicated competitive inhibition of the enzyme. Michaelis-Menten kinetics using secreted acid phosphatases from L. tarentolae incubated with di(isomaltolato)oxovanadium(IV) indicated inhibition on the enzymes, but the mechanism was not clearly determined.

Access Type

Thesis-ISU Access Only

DOI

http://doi.org/10.30707/ETD2017.Wallace.C

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