| Summary |
The endocannabinoid arachidonoyl ethanolamide (AEA) and prostaglandins derived from it selectively induce apoptosis in tumorigenic cell lines due to overexpression of COX-2. It is likely that a novel J-series prostamide, 15-deoxy-[delta]12,14-prostaglandin J2-ethanolamide (15d-PMJ2), is the cytotoxic mediator of AEA-induced apoptosis. Conjugation of a fluorescent group to prostamides of interest may be helpful in determining localization and pharmacokinetic properties needed for clinical development. The synthetic flexibility and bright luminescence of naphthalimides make them attractive probes for this purpose. Previous studies in our labs focused on identifying substituents on naphthalimide that cause minimal interference with intracellular drug localization and metabolism. Those studies indicated that a 4-morpholino naphthalimide would be a suitable probe for conjugation based on its lack of cytotoxicity. Unfortunately, we found that this probe renders AEA inactive, presumably by preventing its cyclization into prostamides. We hypothesize that conjugation of the 4-morpholino naphthalimide to an already-cyclized metabolite, such as 15d-PMJ2, will allow the drug to retain its activity. |
| General note | Presented to the faculty of the Department of Chemistry |
| General note | Advisor: William E. Allen |
| General note | Title from PDF t.p. (viewed February 12, 2019). |
| Dissertation note | M.S. East Carolina University 2018 |
| Bibliography note | Includes bibliographical references. |
| Technical details | System requirements: Adobe Reader. |
| Technical details | Mode of access: World Wide Web. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
