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Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription

Thowfeik, Fathima Shazna
http://orcid.org/0000-0002-0932-3098
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655

Abstract Details

2016, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
Cancer is a major public health problem in the worldwide and second leading cause of death in the United States. The major problem in treatment of cancer is the off target cytotoxicity. Therapeutic selectivity is therefore essential. Evidence suggests that, compared to normal cells, many types of cancer cells have increased level of ROS, a condition known as oxidative stress. Acute myeloid leukemia (AML) is known to possess of elevated levels of ROS, due to the increase expression of NADPH oxidases. Therefore to enhance the selectivity towards cancer we designed and synthesized novel anti-cancer agents that are converted to reactive molecules upon oxidation by ROS. In this study I explored the possible use of reactive oxygen-activated DNA modifying (RAC) agents against AML. A key amine on the lead agent was investigated via cytotoxicity assays and was found necessary for potency. The two best compounds were screened via the NCI-60 cell panel. These two compounds had potency between 200 and 800 nM against many of the leukemia cancer cell types. Subsequent experiments explored activity against a transformed AML model that mimics the molecular signatures identified in primary AML patient samples.
Edward Merino, Ph.D. (Committee Chair)
Patrick Limbach, Ph.D. (Committee Member)
Laura Sagle, Ph.D. (Committee Member)
129 p.
Biochemistry
Reactive Oxygen Species; AML; mechanism of action; cytotoxicity; homologous recombination; HDAC8

Recommended Citations

Citations

  • Thowfeik, F. S. (2016). Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655

    APA Style (7th edition)

  • Thowfeik, Fathima Shazna. Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655.

    MLA Style (8th edition)

  • Thowfeik, Fathima Shazna. "Targeting a Common Enemy: Toxic Cellular Mechanism of Novel Anti-cancer Agents that Alter DNA and Transcription." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460652655

    Chicago Manual of Style (17th edition)

ucin1460652655
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© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.