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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

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