This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
Reactive oxygen species (ROS) are a series of molecules, ions, and radicals derived from oxygen that possess remarkable reactivity. They act as signaling molecules when their concentration in cells is within a normal range. When the levels of ROS increase, reaching a concentration in which the antioxidants cannot readily quench…
Reactive oxygen species (ROS) are a series of molecules, ions, and radicals derived from oxygen that possess remarkable reactivity. They act as signaling molecules when their concentration in cells is within a normal range. When the levels of ROS increase, reaching a concentration in which the antioxidants cannot readily quench them, oxidative stress will affect the cells. These excessive levels of ROS result in direct or indirect ROS-mediated damage of proteins, nucleic acids, and lipids. Excessive oxidative stress, particularly in chronic inflammation, has been linked with mutations and carcinogenesis. One of the main targets of ROS in severe oxidative stress is mitochondrial DNA (mtDNA). The synthesis of analogues of alpha-tocopherol is described as potential compounds with the ability to remediate defective mitochondria. An interesting possibility for eradicating cancer cells is to selectively target them with oxidative species while avoiding any deleterious effects on healthy cells. To accomplish this, analogues of the beta-hydroxyhistidine moiety of the antitumor agent bleomycin (BLM) were synthesized. The first part of this thesis focuses on the synthesis of simplified analogues of alpha-tocopherol. These analogues possess a bicyclic pyridinol as the antioxidant core and an alkyl group as the lipophilic chain to mimic alpha-tocopherol. Additionally, analogues with a completely oxidized pyridinol core were synthesized. Some of these analogues showed promising properties against ROS production and lipid peroxidation. The protection they conferred was shown to be tightly regulated by their concentration. The second part of this thesis focuses on the synthesis of analogues of beta-hydroxyhistidine. BLMs are glycopeptides that possess anticancer activity and have been used to treat testicular carcinomas, Hodgkin's lymphoma, and squamous cell carcinomas. The activity of BLM is based on the degradation of DNA, or possibly RNA, caused by a Fe(II)-BLM complex in the presence of O2. The beta-hydroxyhistidine moiety of BLM contributes to metal coordination via two ligands: the N-3 nitrogen atom of imidazole and possibly the nitrogen atom of the amide. A series of beta-hydroxyhistidine analogues has successfully been synthesized.
