Andrews, Timothy Edward2014-01-162014-01-162013-03https://hdl.handle.net/11299/162298University of Minnesota M.S. thesis. March 2013. Major: Medicinal Chemistry. Advisor: Daniel A. Harki. 1 computer file (PDF); xii, 151 pages, appendix A.Most commercially available chemotherapeutics targeting acute myeloid leukemia (AML) lack the ability to target cancer stem cells, one of the central reasons for cancer relapse. The natural product parthenolide is able to ablate the cancer stem cell population within tumors, which is paramount to it currently being developed as a clinical candidate. Unfortunately, parthenolide is not a perfect therapeutic, its modest potency and poor water solubility hinder its development. The focus of this thesis is to optimize parthenolide as a clinical candidate, by addressing the aforementioned concerns with parthenolide. A parthenolide analogue library was synthesized that varied different parts of the natural product in an effort to enhance the potency and water solubility. In addition, conjugation of parthenolide to a gold nanoparticle delivery system was also investigated as another method to attempt to optimize parthenolide. These alterations will be useful in the continuous development of parthenolide as a promising therapeutic against cancer and specifically cancer stem cells.en-USThesis or Dissertation