Open Access Dissertation
Date of Award
The scope of this thesis is focused towards the development of metal-containing coordination compounds as potential therapeutic agents. Efforts of this research involve the design, synthesis, and purification of these complexes, as well as their evaluation by spectroscopic, spectrometric, and electrochemical characterization. The antineoplastic properties of these metal-containing pro-drugs are tested against the inhibition activity of the 26S proteasome. Selected metal ions ranging from transition to main group elements have been incorporated in various ligand systems containing phenolate and pyridyl donor sets. The mechanistic behavior of these complexes in solution has been thoroughly investigated along with their in vitro anticancer properties against the growth of prostate cancer PC-3 cells. It has been demonstrated that apoptosis induction of the PC-3 cells is due to the inhibition activity of the 26S proteasome upon treatment of various concentrations of these metal-based pro-drugs. The antiproliferative effects of these complexes are highly dependent on the charge, redox activity of the metal ions, as well as the nature of the chelating ligands.
Tomco, Dajena, "Probing Proteasome Inhibition By Metal Copmplexes As A New Route For Anticancer Therapy" (2014). Wayne State University Dissertations. 1078.