Abstract

The objective of this program of the NCDDG, is to discover natural products produced by marine invertebrate animals and/or associated microorganisms which display activity in Wyeth's oncology drug screens. Specifically, this program will: Collect a variety of marine invertebrate animals (~ 300 annually) from different geographical locales and ecological niches in the Philippines and the South Pacific. In addition, microorganisms from marine habitats in Fiji and the surrounding USP region will be isolated and cultured at Wyeth. Microorganisms from the Philippines will be isolated and cultured by Dr. Gomez's group at UP-MSI. All samples will be screened in Wyeth's oncology screens. The organisms that display activity will be re-fermented and supplied for isolation studies. The details of these studies are provided in Drs. Carter and Greenstein's section for the work to be done at Wyeth, and Dr. Gomez's section for the work to be done at UP-MSI. Perform bioassay-guided isolation of active constituents from the extracts of the above mentioned organisms, determine their structures, and provide these metabolites for biological evaluation. Organisms will be prioritized on the basis of screening results from Wyeth's mechanism-based screening protocol. Purified metabolites will be further evaluated in secondary assays to define mechanism of action, and for in vivo efficacy against human solid tumors implanted in nude mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA067786-15
Application #
7810589
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
15
Fiscal Year
2009
Total Cost
$522,243
Indirect Cost

  Institution

Name
University of Utah
Department
Type
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Dalisay, Doralyn S; Williams, David E; Wang, Xiao Ling et al. (2013) Marine sediment-derived Streptomyces bacteria from British Columbia, Canada are a promising microbiota resource for the discovery of antimicrobial natural products. PLoS One 8:e77078
Prasad, Pritesh; Aalbersberg, William; Feussner, Klaus-D et al. (2011) Papuamides E and F, Cytotoxic Depsipeptides from the Marine Sponge Melophlus sp. Tetrahedron 67:8529-8531
Williams, David E; Loganzo, Frank; Whitney, Lauren et al. (2011) Depsides isolated from the Sri Lankan lichen Parmotrema sp. exhibit selective Plk1 inhibitory activity. Pharm Biol 49:296-301
Janso, Jeffrey E; Carter, Guy T (2010) Biosynthetic potential of phylogenetically unique endophytic actinomycetes from tropical plants. Appl Environ Microbiol 76:4377-86
Williams, David E; Yu, Ker; Behrisch, Hans W et al. (2009) Rolloamides A and B, cytotoxic cyclic heptapeptides isolated from the Caribbean marine sponge Eurypon laughlini. J Nat Prod 72:1253-7
Williams, David E; Hollander, Irwin; Feldberg, Larry et al. (2009) Scalarane-based sesterterpenoid RCE-protease inhibitors isolated from the Indonesian marine sponge Carteriospongia foliascens. J Nat Prod 72:1106-9
Whitson, Emily L; Bugni, Tim S; Chockalingam, Priya S et al. (2009) Fibrosterol sulfates from the Philippine sponge Lissodendoryx (Acanthodoryx) fibrosa: sterol dimers that inhibit PKCzeta. J Org Chem 74:5902-8
Roll, Deborah M; Barbieri, Laurel R; Bigelis, Ramunas et al. (2009) The lecanindoles, nonsteroidal progestins from the terrestrial fungus Verticillium lecanii 6144. J Nat Prod 72:1944-8
Whitson, Emily L; Ratnayake, Anokha S; Bugni, Tim S et al. (2009) Isolation, structure elucidation, and synthesis of eudistomides A and B, lipopeptides from a Fijian ascidian Eudistoma sp. J Org Chem 74:1156-62
Bugni, Tim S; Harper, Mary Kay; McCulloch, Malcolm W B et al. (2008) Fractionated marine invertebrate extract libraries for drug discovery. Molecules 13:1372-83

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