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
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/34981 |
| Date | 07 December 1994 |
| Creators | Nagle, Dale George |
| Contributors | Gerwick, William H. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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