The long-term objective of this part of the proposal is to isolate ant-tumor and other bioactive compounds from microalgae, especially those in the lower eukaryotic phyla of Protocista. The proposed work is based on the promising results obtained in the preceding grant period. Discovered and anticipated compounds are macrolides, polyethers, polyoxygenated alkyl compounds, nitrogenous compounds, etc., whose structural types are not seen in other phyla. There are strong indications that some of the highly active trace compounds discovered in marine supply of such compounds from culturable sources. The project leader's group has lengthy experience in culturing microalgae and studying their metabolites and is in possession of a large culture collection and excellent facilities. Specifically, 1. Free-living microalgae belong to Pyrrophyta, Haptophyta, Cryptophyta and Raphidophyta from both temperate and tropical waters and some from inland waters will be cultured in quantity and screened for bioactivities. 2. Organisms symbiotic or associated with marine invertebrates, macro- and microalgae will be isolated, cultured and screened. In particular, the hitherto unculturable organisms known to produce interesting metabolites and have intra-cellular symbionts, such as Cryptophyta organisms in Dinophysis spp., will be focused. 3. Crude, partially purified and pure compounds will be tested in mechanism-based assays at Bristol-Myers Squibb, and their structures will be studied using various physico-chemical methods. Limited in- house cytotoxicity and mechanism-based assays will be performed as quick isolation guides. The structures of pure active compounds will be elucidated by physico-chemical methods including high field NMR. 4. Large-scale culture work will be done using the recently developed facilities to produce enough amounts of compounds with proven activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19CA067775-08S1
Application #
6657052
Study Section
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
8
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Nam, Sang-Jip; GaudĂȘncio, Susana P; Kauffman, Christopher A et al. (2010) Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis. J Nat Prod 73:1080-6
West, Lyndon M; Faulkner, D John (2008) Acanthosulfate, a sulfated hydroxyhydroquinone sesterterpenoid from the sponge Acanthodendrilla sp. J Nat Prod 71:269-71
Martin, Glenroy D A; Tan, Lik T; Jensen, Paul R et al. (2007) Marmycins A and B, cytotoxic pentacyclic C-glycosides from a marine sediment-derived actinomycete related to the genus Streptomyces. J Nat Prod 70:1406-9
Thammana, Sudhakararao; Suzuki, Hideharu; Lobkovsky, Emil et al. (2006) Isolation and structure assignment of an iminotetrasaccharide from a cultured filamentous cyanobacterium Anabaena sp. J Nat Prod 69:365-8
Oh, Dong-Chan; Jensen, Paul R; Kauffman, Christopher A et al. (2005) Libertellenones A-D: induction of cytotoxic diterpenoid biosynthesis by marine microbial competition. Bioorg Med Chem 13:5267-73
Tan, Ren Xiang; Jensen, Paul R; Williams, Philip G et al. (2004) Isolation and structure assignments of rostratins A-D, cytotoxic disulfides produced by the marine-derived fungus Exserohilum rostratum. J Nat Prod 67:1374-82
Rao, M Rama; Faulkner, D John (2004) Botryllamides E-H, four new tyrosine derivatives from the ascidian Botrylloides tyreum. J Nat Prod 67:1064-6
Konishi, Masataka; Yang, Xuemin; Li, Bo et al. (2004) Highly cytotoxic metabolites from the culture supernatant of the temperate dinoflagellate Protoceratium cf. reticulatum. J Nat Prod 67:1309-13
Davies-Coleman, Michael T; Dzeha, Thomas M; Gray, Christopher A et al. (2003) Isolation of homodolastatin 16, a new cyclic depsipeptide from a Kenyan collection of Lyngbya majuscula. J Nat Prod 66:712-5
Garo, Eliane; Starks, Courtney M; Jensen, Paul R et al. (2003) Trichodermamides A and B, cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens. J Nat Prod 66:423-6

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