Date of Award
A number of key studies have shown that the natural product capsaicin displays in vitro and in vivo antitumor effects against a variety of cancers, however, both the analgesic and cancer-related therapeutic potential of capsaicin have been limited by its unpleasant pungent side effects and modest potency. N-acyl vanillylamides (N-AVAMs) are a unique class of compounds that are simple side chain modified capsaicin derivatives. Limited structure-activity relationship (SAR) studies of N-AVAMs demonstrated that substitution of the capsaicin side-chain with longer unsaturated fatty acid groups results in non-pungent analogs with improved anti-invasive activity relative to capsaicin. In an effort to ultimately create and test new analogs for in vitro and in vivo biological evaluation studies this project is centered on the synthesis of rare and unique N-AVAMs composed of -linoleic acid (GLA, 10) and stearidonic acid (SDA, 11), rare -3 fatty acids that are reported to be found in high concentrations in the dietary supplements Echium seed oil and Ahiflower oil. Each of these oils were evaluated indirectly for GLA and SDA content by invoking a chemical capture reaction using the plant oils as stand-alone reagents in a condensation reaction with vanillamine. The products obtained were purified and analyzed using a combination of analytical techniques, including mass spectrometry and NMR spectroscopy. Although the research was disrupted by COVID-19, the preliminary results obtained from these studies suggest that natural product oils may be a valuable source of rare polyunsaturated fatty acids to be used as building blocks in the synthesis of novel N-AVAMs.
Bettiga, Eli, "Synthesis of Novel Long Chain Unsaturated Fatty Acid Analogs of Capsaicin" (2021). Honors Theses. 1785.