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Bisphosphonate and Vanadium-Bisphosphonate Compounds as New Directions in the Treatment of Leishmaniasis
Date of Award
Thesis-ISU Access Only
Master of Science (MS)
Department of Chemistry
Marjorie A. Jones
Sphingolipids are a class of membrane lipids characterized by an 18-carbon amino-alcohol group, the simplest of which are the sphingosine, phytosphingosine and dihydrosphingosine molecules. They are the backbones to which the many other sphingolipids are related. Sphingolipid metabolism is includes a complex network of enzymes that catalyze the synthesis and degradation of the lipids. Of interest in this study was an enzyme that is reported to catabolize two sphingolipids, sphingomyelin and inositol phosphoryl ceramide, in the Leishmania parasite. Others have shown that activity of this enzyme in Leishmania, a neutral sphingomyelinase (nSMase) enzyme known as ISCL, is required for the pathogen's growth and virulence. Leishmania are parasitic protozoan that cause the disease leishmaniasis, a tropical disease which is a significant problem in many countries. Several studies have indicated that bisphosphonate compounds are potent inhibitors of SMase activity. This study tested several newly available bisphosphonate and vanadium-bisphosphonate compounds on nSMase activity isolated from Bacillus cereus (as a model system) and on the growth of Leishmania tarentolae. Data indicate nSMase from Bacillus cereus is completely inhibited by some of these compounds in the millimolar range when compared to the control enzyme reaction. Data also indicate a significant adverse effect of the compounds on the parasite, although the parasite's nSMase enzyme, ISCL, appeared not to be affected.
Christensen, Amy, "Bisphosphonate and Vanadium-Bisphosphonate Compounds as New Directions in the Treatment of Leishmaniasis" (2014). Theses and Dissertations. 205.
Imported from ProQuest Christensen_ilstu_0092N_10307.pdf