The overall goal of this research program is to describe structurally- novel neurotoxins from marine algae and cyanobacteria which can serve as neurochemical probes in mammalian pharmacology and provide new lead compounds for the pharmacotherapy of various human illnesses.
The specific aims and methods for this project begin with the screening of a large number of marine algal extracts in a battery of assays which are designed to detect neurotoxic substances. The primary screening will occur at both performance sites and be composed of a complementary mixture of mechanism-based and mechanism-blind assays. The algal extracts derive from a repository at OSU containing more than 1000; in addition, approximately 100 new collections of algae are made yearly by shallow water SCUBA methods and extracted according to standardized protocols. Following initial dereplication efforts, active extracts will be chromatographed and then followed by re-evaluation of the fractions in the appropriate bioassays. Pure and active compounds resulting from the bioassay-driven isolation process will be subjected to structure elucidation utilizing modern NMR techniques in concert with mass spectrometry and other spectroscopic methods. The pharmacological mechanism of action of new neurotoxins will be determined using a battery of receptor binding and other neurochemical assays. The chemical and pharmacological portfolio's of these newly discovered neurotoxins will be shared with the appropriate pharmaceutical companies for potential development in the areas of epilepsy and neurodegenerative disorders, and when possible, new neurotoxins will be made generally available to the biomedical community. Through established collaborations with various industrial partners, and the NOVASCREEN(R) program, development of these neurotoxins as potential therapeutics will occur as appropriate.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063554-04
Application #
6761018
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Schwab, John M
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$277,076
Indirect Cost
Name
Oregon State University
Department
Type
Schools of Pharmacy
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339
Sabry, Omar M; Goeger, Douglas E; Gerwick, William H (2017) Biologically active new metabolites from a Florida collection of Moorea producens. Nat Prod Res 31:555-561
Sabry, Omar M M; Goeger, Douglas E; Valeriote, Frederick A et al. (2017) Cytotoxic halogenated monoterpenes from Plocamium cartilagineum. Nat Prod Res 31:261-267
Sabry, Omar M M; Goeger, Douglas E; Gerwick, William H (2017) Bioactive new metabolites from the green alga Udotea orientalis growing on the Gorgonian coral Pseudopterogorgia rigida. Nat Prod Res 31:1245-1250
McPhail, Kerry L; Correa, Jhonny; Linington, Roger G et al. (2007) Antimalarial linear lipopeptides from a Panamanian strain of the marine cyanobacterium Lyngbya majuscula. J Nat Prod 70:984-8
Gross, Harald; Goeger, Douglas E; Hills, Patrice et al. (2006) Lophocladines, bioactive alkaloids from the red alga Lophocladia sp. J Nat Prod 69:640-4
Han, Bingnan; Gross, Harald; Goeger, Douglas E et al. (2006) Aurilides B and C, cancer cell toxins from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. J Nat Prod 69:572-5
LePage, Keith T; Dickey, Robert W; Gerwick, William H et al. (2005) On the use of neuro-2a neuroblastoma cells versus intact neurons in primary culture for neurotoxicity studies. Crit Rev Neurobiol 17:27-50
Sabry, Omar M M; Andrews, Simeon; McPhail, Kerry L et al. (2005) Neurotoxic meroditerpenoids from the tropical marine brown alga Stypopodium flabelliforme. J Nat Prod 68:1022-30
Andrianasolo, Eric H; Gross, Harald; Goeger, Douglas et al. (2005) Isolation of swinholide A and related glycosylated derivatives from two field collections of marine cyanobacteria. Org Lett 7:1375-8
LePage, K T; Goeger, D; Yokokawa, F et al. (2005) The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons. Toxicol Lett 158:133-9

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