) The objective of this sub-program of the NCDDG, to discover natural products produced by marine invertebrate animals andor associated microorganisms which display activity in W AR's oncology drug screens, remains essentially the same as in the original grant application, though as stated in the overview section, the approaches to achieving this objective continue to evolve.
The specific aims developed to accomplish this objective are described below: 1. To collect a variety of marine invertebrate animals from different geographical locales and ecological niches. The samples (about 300 annually) will be obtained from the Philippines as part of a collaboration with Dr. Edgardo Gomez, Director UP-MSI and the Fiji Islands and surrounding region as part of a collaboration with Dr. William Aalbersberg, Professor of Chemistry, University of the South Pacific. 2. Microorganisms from marine habitats will be isolated and cultured at WAR. The organisms that display activity will be re-fermented and supplied for isolation studies. The details of these studies are provided in Drs. Maiese and Greenstein's section. 3. To perform bioassay guided isolation of active constituents from the extracts of the above mentioned organisms and to provide these metabolites for biological evaluation. Organisms will be prioritized on the basis of screening results from WAR'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. 4. To structurally characterize the active constituents from the above mentioned organisms. 5. To continue preclinical studies with the makaluvamines and neoampimedine, two classes of marine natural products identified as priorities during the first grant period.
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