Wang, Dan2015-06-152015-06-152013-03https://hdl.handle.net/11299/172626University of Minnesota Master of Science thesis. March 2013. Major: Medicinal Chemistry. Advisor: Dr. Daniel A. Harki. 1 computer file (PDF); xiv, 211 pages.Cancer stem cells (CSCs), also known as tumor-propagating cells or tumor-initiating cells, are subpopulations of undifferentiated, highly tumorigenic cells found within bulk tumors. The rapid advances of cancer research and development of relative technologies have provided more and more evidence for the existence of CSCs, as well as the important roles they play in drug resistance and disease relapse of cancer. However, because of their quiescent nature and the similarities to normal stem cells, eradicating CSCs presents a challenging task. Chapter one provides an overview of cell surface markers of CSCs. Those markers are potential diagnostic macromolecules and targets for drug delivery.Parthenolide (PTL) is a sesquiterpene lactone natural product isolated from Mexican Indian medicinal herb Tanacetum parthenum (feverfew plant), a known medical herb utilized for centuries. PTL has been extensively studied as an anticancer agent, showing significant efficacy towards a wide spectrum of human cancer cells. In 2005, the identification of PTL as the first stand-alone and selective cytotoxic agent against the acute myeloid leukemia CSCs further heightened its therapeutic potential. However, the mechanism of action of PTL's CSC inhibitory activity is still an area of debate. Our efforts to elucidate the molecular targets of PTL is described in chapter two. The design and synthesis of two PTL affinity probes with diverse biological activity as well as their utilization in comparative and competitive protein pull-down experiments to enrich the cellular protein targets of PTL is presented. Although exhibiting promising anticancer and anti-CSC activities, the modest biological potency and poor water solubility prevent further development of PTL. Chapter three describes our efforts to synthesize PTL analogues, as well as our strategy to prepare water-soluble PTL prodrugs.enCancer stem cellsClick chemistryNatural product modificationParthenolideProtein pull-downProteomicsMedicinal chemistryThesis or Dissertation