Full metadata
Title
Synthesis of benzoquinone antioxidants and a bleomycin disaccharide library
Description
Healthy mitochondria are essential for cell survival. Described herein is the synthesis of a family of novel aminoquinone antioxidants designed to alleviate oxidative stress and prevent the impairment of cellular function. In addition, a library of bleomycin disaccharide analogues has also been synthesized to better probe the tumor targeting properties of bleomycin. The first study involves the synthesis of a benzoquinone natural product and analogues that closely resemble the redox core of the natural product geldanamycin. The synthesized 5-amino-3-tridecyl-1,4-benzoquinone antioxidants were tested for their ability to protect Friedreich's ataxia (FRDA) lymphocytes from induced oxidative stress. Some of the analogues synthesized conferred cytoprotection in a dose-dependent manner in FRDA lymphocytes at micromolar concentrations. The biological assays suggest that the modification of the 2-hydroxyl and N-(3-carboxypropyl) groups in the natural product can improve its antioxidant activity and significantly enhance its ability to protect mitochondrial function under conditions of oxidative stress. The second project focused on the synthesis of a library of bleomycin disaccharide-dye conjugates and monitored their cellular uptake by fluorescence microscopy. The studies reveal that the position of the carbamoyl group plays an important role in modulating the cellular uptake of the disaccharide. It also led to the discovery of novel disaccharides with improved tumor selectivity.
Date Created
2013
Contributors
- Mathilakathu Madathil, Manikandadas (Author)
- Hecht, Sidney M. (Thesis advisor)
- Rose, Seth (Committee member)
- Woodbury, Neal (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
x, 188 p. : ill
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.16427
Statement of Responsibility
by Manikandadas Mathilakathu Madathil
Description Source
Retrieved on Oct. 18, 2013
Level of coding
full
Note
thesis
Partial requirement for: Ph.D., Arizona State University, 2013
bibliography
Includes bibliographical references (p. 178-188)
Field of study: Chemistry
System Created
- 2013-03-25 01:40:48
System Modified
- 2021-08-30 01:43:16
- 3 years 2 months ago
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