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Creators: Wagner, Carl

COMBATING CANCER AND ALZHEIMER'S DISEASE: SYNTHESIS OF NOVEL, CHEMOTHERAPEUTIC REXINOIDS

Description

The FDA-approved drug bexarotene has been predominantly utilized for the treatment of cutaneous T-cell lymphoma (CTLC), but has shown promise as an off label treatment for various other cancers as well as Alzheimer's disease (AD). However, harmful side effects such as hypothyroidism have catalyzed a search for alternative rexinoids which retain similar levels of RXR agonism while reducing the undesirable effects incurred by bexarotene. This honors thesis outlines the steps taken to design and synthesize novel analogues of the selective retinoid-X-receptor (RXR) agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene). Corresponding NMR spectra indicates the successful construction of four novel compounds which are structurally similar to known, biologically-evaluated rexinoids that have induced fewer side effects while stimulating greater levels of RXR selectivity as compared to bexarotene. Future In vitro analyses of these four analogues coupled with the recognized efficacy of their parent compounds demonstrate the chemotherapeutic potential of structurally modified bexarotene analogues

ContributorsDavidson, Jesse Raymond (Author) / Wagner, Carl (Thesis director) / Ball, Rebecca (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2016-05

Treatment for T-Cell Lymphoma Cancer: Synthesis of Analog Compound of Bexarotene

Description

Cancer, a disease which affects many lives, has been the topic of interest for this research. Treatment options are often available to help lessen the effects of the disease and in regards to cutaneous T-cell lymphoma (CTCL), no cure currently exists. An FDA approved drug by the name of Bexarotene has been developed to provide chemotherapeutic effects within CTCL. Bexarotene has also been used in trials of breast cancer, lung cancer, glioblastoma multiforme and various neurodegenerative diseases. Yet the medication often causes serious side effects including hyperthyroidism, raised triglyceride levels and cutaneous toxicity. The focus of this research is to synthesize a hydroxylated analog compound of Bexarotene in efforts to produce a molecule that provides better chemotherapeutic effects while also lessening the various side effects caused. Synthesis of the molecule followed various organic chemistry techniques and reactions to create the final product. Melting point analysis, NMR and other various characterization data helped to confirm the synthesis of the intended molecule. Preliminary bioassay data results of the analog compound showed similar potency to that of Bexarotene. Further testing, however, will be required to determine the full pharmacokinetic profile of the molecule. Future direction of the research focuses on both further testing of the hydroxylated analog as well synthesizing newer analog compounds to find a molecule that can provide the best effects within cutaneous T-cell lymphoma and the various other diseases as well.

ContributorsMinasian, Ani Christina (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Social and Behavioral Sciences (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)

Created2018-05