Graduation Year
2026
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Chemistry
Major Professor
Bill J. Baker, Ph.D.
Committee Member
Theresa Evans-Nguyen, Ph.D.
Committee Member
H. Lee Woodcock, Ph.D.
Committee Member
Frederick Valeriote, Ph.D.
Keywords
keymarazoles, Maigheotides, malaria, myxillosides, zebrafish embryos, natural products, structural-activity relationship
Abstract
Society’s perpetual need for new disease treatments continuously leans on the shouldersof willing researchers. Even in modern day, many described diseases lack a cure or a symptomatic treatment; worse yet, the necessity for new drugs is amplified with rises in drug- resistant microbial infections, such as methicillin-resistant Staphylococcus aureus (MRSA). Historically, remedies and disease treatments have been rooted in the medicinal properties of plants and animals; naturally derived analgesics, like milk of the poppy or willow bark tea, date back thousands of years. With the developments of modern medicine, drug discovery, and natural product researchers found a wealth of potential in marine organisms. Sessile marine invertebrates, most notably corals and sponges, that lack physical defense mechanisms instead rely on chemical defenses for survival. The abundance of secondary metabolites in these organisms makes them key targets of natural product researchers.
The elucidation of unknown chemical compounds is dependent not only on knowing the elemental composition but also on knowing how each atom is linked within the molecule. Breakthroughs in chemical analysis during the 1700 to 1800s built the basic foundations we use in modern chemistry; however, early chemists were still limited to the knowledge and technology of their time. Modern natural product chemists take full advantage of the technological advances in current research. Developments in mass spectrometry, nuclear magnetic resonance, and X-ray crystallography provide the resolution and sensitivity needed to elucidate larger and more complex metabolites.
The studies described here focus on the investigation of new chemistry isolated and elucidated from marine invertebrates collected from various marine ecosystems: tropical, deep- sea, and cold, shallow water environments. The first study was conducted on a deep-sea black coral, Phanopathes, revealing four new linear peptides, maigheotides A-D (2.1-2.4). Structural similarities of these peptides to known neural peptides suggest their biological function could be related to the regulation of G protein-coupled receptors. The second study was focused on four new alkaloids isolated from a red sponge collected in the Florida Keys, keymarazoles A-D (3.1- 3.4). A new synthetic route was used to synthesize all four naturally occurring alkaloids and 25 undescribed analogs. The biological screening revealed keymarazole analogs with longer ester groups increased inhibition against malaria. The natural products 3.1, 3.2, and 3.3 also had dramatic effects on zebrafish embryonic development. The final study describes the isolation and elucidation of seven new ω-glycosylated fatty acid amides, myxillosides A-G (4.1-4.7), from the Antarctic sponge Myxilla. Biological activity of myxillin-class structures showed promising anti-inflammatory effects, consistent with previous studies.
Scholar Commons Citation
Smith, Benjamin Reed, "From the Tropics to the Poles: Chemical Investigation of Marine Invertebrates through Elucidation and Synthesis" (2026). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/11418
