My investigations of the natural products of marine algae have resulted in the discovery of several new secondary metabolites. Bioassay-guided fractionation led to the isolation of these new compounds and spectroscopic analysis was utilized in their structural characterization. Two new and potent antimitotic metabolites, curacins B and C, were isolated from a Curacao collection of Lyngbya majuscula. In addition, four curacin A analogs were prepared by semisynthetic methods. The structures of the new curacins and the curacin A analogs were determined by spectroscopic analysis in comparison with curacin A. The biological properties of the new natural products and synthetic derivatives of curacin A were examined. Investigations of another Curacao collection of L. majuscula revealed a new cytotoxic lipopeptide, microcolin C. Microcolin C was found to have an interesting profile of cytotoxicity to human cancer-derived cell lines. A new metabolite, vidalenolone, was isolated from an Indonesian red alga Vidalia sp. The structure of this new cyclopentenolone-containing compound was determined by a combination of spectroscopic methods. Filamentous cells isolated from female gametophytes of the brown alga Laminaria saccharina were cultured in flasks or bioreactors. These cultures produced a variety of w6-lipoxygenase metabolites: 13-hydroxy-9,11-octadecadienoic acid (13-HODE), 13-hydroxy-6,9,11,15-octadecatetraenoic acid (13-HODTA), and 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE). Five oxidized anandamide derivatives were prepared from anandamide through autoxidation in an exploration of ligand binding to the cannabinoid receptor. Their structures were determined by a combination of NMR spectroscopy and GC-MS. The cannabinoid receptor binding affinity of these derivatives was evaluated. This study revealed the following trend in activity: anandamide > 15- > 9- > 8- > 11- > 5-hydroxyanandamide. / Graduation date: 1998

Marine algae have been recognized as a rich resource of new and unusual organic molecules with diverse biological properties. The current need to develop new antifungal, anticancer, antibiotic and antiviral drugs has led to an intense research effort into the discovery, isolation and structure determination of potential medicinal agents from marine algae. In the past two years, I have participated in a drug discovery program designed for antitumor, antifungal and other agents of potential pharmaceutical utility from the marine cyanobacterium Lyngbya majuscula. This research utilized modern chromatographic and spectrochemical techniques including 2D NMR spectroscopy. Brine shrimp toxicity guided the fractionation that led to the discovery of the biologically active compound kalkitoxin from a Curacao Lyngbya majuscula extract. The structure of this new thiazoline ring-containing lipid was determined spectroscopically by interpretation of 2D-NMR experiments, including heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple-bond coherence spectroscopy (HMBC) and ��H-��H COSY at room temperature and elevated temperature. Kalkitoxin shows modest molluscicidal toxicity, good brine shrimp toxicity and extremely potent ichthyotoxicity. From the same extract of Lyngbya majuscula, I also isolated two other secondary metabolites, malyngamide J and malyngamide L. The structures of these new compounds, including stereochemistry, were determined by spectroscopic techniques including 2D-NMR experiments and by comparison with other known malyngamides. / Graduation date: 1997

I have participated in a drug discovery program designed to screen marine algae for inhibitors of cancer-related enzymes, antitumor compounds, antiinflammatory substances, and other agents of potential pharmaceutical utility. Over 1,500 lipid and aqueous extracts of marine plants and animals were surveyed for biomedical potential. Assays designed to screen extracts for new types of marine toxins have served to guide the isolation and identification of biologically active compounds. Extracts of the Oregon marine alga Constantinea simplex were found to contain a mixture of constanolactones, and lactonized cyclopropyl-containing oxylipin metabolites that logically derive from arachidonic and eicosapentaenoic acids. Spectroscopic analysis and chiroptical measurements of the natural products and various synthetically produced derivatives afforded the structures of seven structurally related compounds. Nakienones A-C and nakitriol, a series of reactive cytotoxic metabolites, were isolated from dead and necrotic branches of stony coral (Acropora sp.) which were completely covered with a gray-black mat of cyanobacteria (Synechocystis sp.). Their structures were determined spectroscopically by interpretation of 2D-NMR experiments, including heteronuclear multiple-bond coherence spectroscopy (HMBC) and 2-D nuclear Overhauser exchange spectroscopy (NOESY), and by comparison with model compounds. Bioassay-guided fractionation of the organic extract of a Curacao Lyngbya majuscula organic extract led to the isolation of an extremely potent brine shrimp toxin with antiproliferative activity. The structure of this new thiazoline ring-containing lipid, curacin A, was deduced from spectroscopic information and comparison of products obtained from chemical degradation of the natural product with the same substances prepared by synthesis. Curacin A is an antimitotic agent that inhibits microtubule assembly and the binding of colchicine to tubulin. In addition to curacin A, a potent new ichthyotoxic depsipeptide (antillatoxin), a new malyngamide derivative, and an unusual molluscicidal compound have been isolated from this alga. / Graduation date: 1995

Thesis (Ph. D.)--University of Hawaii at Manoa, 2003. / Includes bibliographical references (leaves 190-210). Also available via World Wide Web.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2003. / Includes bibliographical references (leaves 190-210).

Thesis (Ph.D.) - James Cook University, 2007. / Typescript (photocopy) Bibliography: leaves 183-195.

Thesis (Ph.D.)--University of Wyoming, 2008. / Title from PDF title page (viewed on August 9, 2009). Includes bibliographical references (p. 113-116).

Thesis (Ph.D.)--Ohio University, March, 2010. / Title from PDF t.p. Includes bibliographical references.

Thesis (M.BmedSc.)--Victoria University of Wellington, 2010. / Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.