DESCRIPTION (provided by applicant): The over-arching goal of this work is to discover new lead compounds from Panamanian microorganisms for the treatment of cancer, CNS disorders, tropical diseases, and agricultural pests, employing a spectrum of innovative as well as traditional bioassays. This pursuit will be inextricably connected to the development of scientific training and capacity building in a biodiversity-rich yet economically-developing country, and will foster tangible results in biodiversity conservation and infrastructure development.
The specific aims of this proposal which will allow us to reach these goals are: 1) Use ecological concepts to guide the collection and culture of endophytic fungi, cyanobacteria and other heterotrophic bacteria within the biodiversity-rich country of Panama, 2) Produce extracts of these collected and cultured materials and prefractionate these by appropriate techniques to produce reduced complexity screening units which have active ingredients in increased titer, 3) Through efforts of personnel in AP2 plus our collaborators, to perform biological screens of extracts, prefractionated extracts, and pure compounds in the following therapeutic areas: Cancer, Central Nervous System biology, Agriculture, and Tropical diseases (malaria, leishmania and Chagas'disease), 4) Utilize an integrated approach of taxonomy, computer databases, and LC-MS data to rapidly and efficiently dereplicate known and nuisance compounds at early stages in the discovery process, 5) Isolate active compounds identified in the above assay areas using bioassay-guided approaches, and to characterize these substances using efficient and modern spectroscopic methods, 6) Inventory the biodiversity of terrestrial plants and marine algae in Panama, and to continue to build the permanent floral collections in Panama, 7) Evolve and maintain the formal contracts between all of the participants in this program to address intellectual property rights, promote equitable sharing of benefits, and to facilitate broad access to the data and results of these research endeavors, 8) Help build the scientific infrastructure and expertise necessary to support a sustainable drug discovery program based in Panama, and 9) Integrate our drug discovery and conservation efforts to develop innovative new economic products from the biodiverse marine and terrestrial habitats of Panama. This proposal seeks to discover new medicines from Panama's rich biodiversity of terrestrial and marine microorganisms. The focus of our discovery efforts are new treatments for cancer, CNS disorders, and tropical diseases as well as agricultural chemicals.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZRG1-ICP2-B (52))
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Katz, Flora N
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Smithsonian Institution
United States
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Moree, Wilna J; McConnell, Oliver J; Nguyen, Don D et al. (2014) Microbiota of healthy corals are active against fungi in a light-dependent manner. ACS Chem Biol 9:2300-8
Coronado, Lorena M; Nadovich, Christopher T; Spadafora, Carmenza (2014) Malarial hemozoin: from target to tool. Biochim Biophys Acta 1840:2032-41
Carneiro, Vania M T; Avila, Carolina M; Balunas, Marcy J et al. (2014) Coibacins A and B: total synthesis and stereochemical revision. J Org Chem 79:630-42
Miller, Bailey; Friedman, Aaron J; Choi, Hyukjae et al. (2014) The marine cyanobacterial metabolite gallinamide A is a potent and selective inhibitor of human cathepsin L. J Nat Prod 77:92-9
Almeida, C; Ortega, H; Higginbotham, S et al. (2014) Chemical and bioactive natural products from Microthyriaceae sp., an endophytic fungus from a tropical grass. Lett Appl Microbiol 59:58-64
Higginbotham, Sarah; Wong, Weng Ruh; Linington, Roger G et al. (2014) Sloth hair as a novel source of fungi with potent anti-parasitic, anti-cancer and anti-bacterial bioactivity. PLoS One 9:e84549
Ortega, Humberto E; Teixeira, Eliane de Morais; Rabello, Ana et al. (2014) Anti-L. donovani activity in macrophage/amastigote model of palmarumycin CP18 and its large scale production. Nat Prod Commun 9:95-8
Winnikoff, Jacob R; Glukhov, Evgenia; Watrous, Jeramie et al. (2014) Quantitative molecular networking to profile marine cyanobacterial metabolomes. J Antibiot (Tokyo) 67:105-12
Ortega, Humberto E; Graupner, Paul R; Asai, Yumi et al. (2013) Mycoleptodiscins A and B, cytotoxic alkaloids from the endophytic fungus Mycoleptodiscus sp. F0194. J Nat Prod 76:741-4
Hau, Andrew M; Greenwood, Jeffrey A; Lohr, Christiane V et al. (2013) Coibamide A induces mTOR-independent autophagy and cell death in human glioblastoma cells. PLoS One 8:e65250

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