| This dissertation describes the chemical structures and biological properties of organic molecules isolated from two marine sources: sponges and marine-derived fungi. The structures of novel compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high resolution mass spectrometry, circular dichroism, and optical rotation data. Sophisticated bioassays were utilized to evaluate the therapeutic effects of these secondary metabolites, including anticancer, antimicrobial, antiparasitic, antiviral, and protein inhibition.;Chapter 1 outlines the history of marine natural products research, important methods used in this field, and applications of marine-derived small molecules as therapeutics and chemical probes. This chapter closes with a discussion of future strategies for drug development from marine natural products, including genomic approaches. The second chapter focuses on a family of common fungal metabolites, diketopiperazines, and their evaluation as growth inhibition agents against the parasite Trypanosoma brucei. This small library of thirteen natural compounds was isolated from two deep water sediment-derived fungal strains, and five semi-synthetic derivatives were also prepared. A discussion of epigenetic experiments to modify secondary metabolite production in filamentous fungi is also included in Chapter 2. The following chapter covers the structural elucidation of four new depsipeptides from the sponge Jaspis splendens. These unique compounds are potent inhibitors of actin, making them interesting candidates for cancer therapy. Chapter 4 highlights the use of data analysis in real time (DART) mass spectrometry in detecting halogenated natural products from a marine-invertebrate derived fungus, Malbranchea graminicola. Two novel chlorinated compounds were identified, and two new brominated analogues were also produced by enriching the growth medium with bromine salts. |
