The long-term objective of this part of the proposal is to develop antitumor, antiviral, an antimicrobial drugs from microalgal sources. The proposal is based on the recent findings of the occurrence of promising compounds in dinoflagellates and other microalgae. Anticipated compounds include polyethers, macrolides, other polyoxygenated compounds, cyclic peptides and depsipeptides. There are strong indications that many of the unique metabolites found in marine invertebrates are actually derived from microalgae. The applicant's group has lengthy experience in culturing microalgae and studying their secondary metabolites and is in possession of a vast collection of unexamined microalgal strains. Specifically, l. Free-living dinoflagellates, diatoms, algae in Chrysophyta, and other microalgae from both temperate and tropical waters, and some from freshwater, will be collected, cultured and screened for the bioactivity. 2. Organisms of the above classes symbiotic or associated with marine invertebrates and algae will be isolated, cultured and screened. 3. Active compounds will be isolated, and the structures of the purified compounds will be studied by physico-chemical methods including high field NMR, mass spectroscopy, and X-ray crystallography. Antitumor and antiviral assays and further development of drugs will be conducted by Bristol-Myers Squibb Co., but limited in-house cytotoxicity and antimicrobial tests will be performed as quick isolation guides.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19CA067775-01
Application #
3731784
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1995
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
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
Lerch, Melissa L; Harper, Mary Kay; Faulkner, D John (2003) Brominated polyacetylenes from the Philippines sponge Diplastrella sp. J Nat Prod 66:667-70

Showing the most recent 10 out of 21 publications