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Each year, millions of people are diagnosed with cancer. In order to fight back, countless drugs are currently being developed as possible treatments for the disease. Histone deacetylase (HDAC) inhibitors are chemical compounds that can be used to reverse repressed transcription of tumor suppressor genes. They are currently used to treat several targeted cancers, but there is much room for improvement to make them work more efficiently without causing unwanted side effects. The aim of our research was to investigate new metal-binding groups to be incorporated into HDAC inhibitors and make them more class or isoform selective. In order to do this, we obtained several compounds predicted to successfully bind with zinc (Zn2+) ions and analyzed their chelating ability using nuclear magnetic resonance and ultraviolet spectroscopy. We also performed several reactions aimed at synthesizing an HDAC inhibitor with the new metal-binding group attached. Our research identified that several groups tested possessed significant ability to bind to Zn2+. Moving forward, once the metal-binding groups are incorporated, the compounds can be tested on cancer cells to determine their ability to inhibit cell growth.
histone deacetylase inhibitor; HDAC; anti-cancer drug; synthesis; spectroscopy
Medicinal and Pharmaceutical Chemistry
L.M. Viranga Tillekeratne
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College of Pharmacy and Pharmaceutical Sciences
Medicinal and Biological Chemistry
The University of Toledo
Digital Initiatives, University of Toledo Libraries
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McDaniel, Jade and Tillekeratne, L. M. Viranga Dr., "Investigation of New Metal-Binding Groups For Histone Deacetylase Inhibitors" (2018). Scholars' Celebration: Undergraduate Research Showcase. 6.
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