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)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-ICP2-B (52))
Program Officer
Katz, Flora N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Smithsonian Institution
United States
Zip Code
Huang, Kuan-Chun; Chen, Zhihong; Jiang, Yimin et al. (2016) Apratoxin A Shows Novel Pancreas-Targeting Activity through the Binding of Sec 61. Mol Cancer Ther 15:1208-16
Lax, Neil C; Ahmed, Kh Tanvir; Ignatz, Christopher M et al. (2016) Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice. Pharm Biol 54:2723-2731
Bertin, Matthew J; Demirkiran, Ozlem; Navarro, Gabriel et al. (2016) Kalkipyrone B, a marine cyanobacterial ?-pyrone possessing cytotoxic and anti-fungal activities. Phytochemistry 122:113-118
Fenner, Amanda M; Engene, Niclas; Spadafora, Carmenza et al. (2016) Medusamide A, a Panamanian Cyanobacterial Depsipeptide with Multiple ?-Amino Acids. Org Lett 18:352-5
Serrill, Jeffrey D; Wan, Xuemei; Hau, Andrew M et al. (2016) Coibamide A, a natural lariat depsipeptide, inhibits VEGFA/VEGFR2 expression and suppresses tumor growth in glioblastoma xenografts. Invest New Drugs 34:24-40
Gromek, Samantha M; deMayo, James A; Maxwell, Andrew T et al. (2016) Synthesis and biological evaluation of santacruzamate A analogues for anti-proliferative and immunomodulatory activity. Bioorg Med Chem 24:5183-5196
Wang, Mingxun; Carver, Jeremy J; Phelan, Vanessa V et al. (2016) Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol 34:828-837
Nabika, Ryota; Suyama, Takashi L; Hau, Andrew M et al. (2015) Synthesis and biological evaluation of the [d-MeAla(11)]-epimer of coibamide A. Bioorg Med Chem Lett 25:302-6
Shao, Chang-Lun; Linington, Roger G; Balunas, Marcy J et al. (2015) Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta. J Org Chem 80:7849-55
Kurita, Kenji L; Glassey, Emerson; Linington, Roger G (2015) Integration of high-content screening and untargeted metabolomics for comprehensive functional annotation of natural product libraries. Proc Natl Acad Sci U S A 112:11999-2004

Showing the most recent 10 out of 77 publications