This application is a continuation of grant 2 RO 1 CA 36622 entitled """"""""Antineoplastic Agents from Marine Organisms."""""""" The funding requested is for years 19-23 of the program. The primary aims of this program remain the same and are 1) to identify new structural classes of natural products produced by marine organisms and evaluate their potential as cancer chemotherapy agents and 2) to continue studies directed at development of new screening protocols for discovery of natural product antitumor agents. Activities in year 19 will focus on completion of ongoing studies, specifically, chemical investigations of approximately 400 samples collected in Kandavu (southern Fiji Islands) and Brazil (Sao Sebastiao, Bahia and Ferdinand de Noronha) between June 1999 and October 2000. In addition, studies will be completed on the mechanism of action and in vivo efficacy of neoamphimedine, deoxyamphimedine, naarnadine A, the patellazoles, and Jaspis johnstoni and Ircinia sp. (the active leads from a p21/p53-FACS assay). During years 20-23, approximately 200 new organisms per year will be collected from a variety of locations including the Solomon Islands, Brazil, Kiribati and Turkey. These samples will also be prioritized based on results from the 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. Assay development studies in the current award period will focus on a p21/p53 screen and an EGFR cDNA microarray assay. In years 15-18 substantial progress was made on all of the specific aims proposed for that cycle. These studies are summarized in the progress report. This work resulted in 20 publications and two patents.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Fu, Yali
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University of Utah
Schools of Pharmacy
Salt Lake City
United States
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Thorson, Megan K; Van Wagoner, Ryan M; Harper, Mary Kay et al. (2015) Marine natural products as inhibitors of cystathionine beta-synthase activity. Bioorg Med Chem Lett 25:1064-6
Sandoval, Imelda T; Manos, Elizabeth J; Van Wagoner, Ryan M et al. (2013) Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F. Chem Biol 20:753-63
Sun, Han; Reinscheid, Uwe M; Whitson, Emily L et al. (2011) Challenge of large-scale motion for residual dipolar coupling based analysis of configuration: the case of fibrosterol sulfate A. J Am Chem Soc 133:14629-36
Dolan, Brian P; Li, Lily; Veltri, Charles A et al. (2011) Distinct pathways generate peptides from defective ribosomal products for CD8+ T cell immunosurveillance. J Immunol 186:2065-72
Lu, Zhenyu; Van Wagoner, Ryan M; Harper, Mary Kay et al. (2011) Mirabamides E-H, HIV-inhibitory depsipeptides from the sponge Stelletta clavosa. J Nat Prod 74:185-93
Pimentel-Elardo, Sheila M; Buback, Verena; Gulder, Tobias A M et al. (2011) New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities. Mar Drugs 9:1682-97
Lu, Zhenyu; Ding, Yuanqing; Li, Xing-Cong et al. (2011) 3-bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian. Bioorg Med Chem 19:6604-7
Wei, Xiaomei; Henriksen, Niel M; Skalicky, Jack J et al. (2011) Araiosamines A-D: tris-bromoindole cyclic guanidine alkaloids from the marine sponge Clathria (Thalysias) araiosa. J Org Chem 76:5515-23
Lu, Zhenyu; Van Wagoner, Ryan M; Harper, Mary Kay et al. (2010) Two ring-A-aromatized bile acids from the marine sponge Sollasella moretonensis. Nat Prod Commun 5:1571-4
Wei, Xiaomei; Bugni, Tim S; Harper, Mary Kay et al. (2010) Evaluation of pyridoacridine alkaloids in a zebrafish phenotypic assay. Mar Drugs 8:1769-78

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