Tropical Disease Drug Discovery from Marine Cyanobacteria in Panama

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DESCRIPTION (provided by applicant): Tropical parasitic and infectious diseases (e.g., malaria, Chagas' disease, leishmaniasis, and Dengue fever) pose enormous global health threats, but are largely ignored by the major pharmaceutical companies. Treatments for tropical diseases are generally prohibitively expensive for many people living in areas of high rates of infection. Furthermore, many tropical diseases are developing resistance to currently available treatments, or are without effective treatments. Natural products contain highly diverse structures with unique characteristics not readily accessible through synthetic or combinatorial chemistry. The hypothesis for this research is that marine species from the biologically diverse oceans in Panama will yield chemically diverse compounds, some of which will inhibit the infection and/or spread of tropical diseases. These new active compounds from marine cyanobacteria may also provide increased efficacy, ability to overcome resistance, and/or reduced side effects as compared with existing agents, and thus could be appropriate for future preclinical and clinical development. The International Cooperative Biodiversity Group (ICBG) based in Panama entitled "Ecologically Directed Drug Discovery in Panama" has been involved in a nine year effort, working to identify treatments for malaria, Chagas' disease, leishmaniasis, and cancer. New collections of marine specimens are needed to continue the search for improved, less expensive treatments for tropical diseases. Thus, the following specific aims (SA) are proposed: SA 1, use ecologically guided marine collection techniques to collect specimens for screening; SA 2, extract marine specimens, perform pre-fractionation of extracts, and send for screening for in vitro activity against tropical diseases including malaria, Chagas' disease, and leishmaniasis, as well as for cytotoxicity testing - prioritize fractions for further analysis based on bioassay results: fractions that exhibit potent activity in one assay with minimal effect on other assays and with corresponding low cytotoxicity will continue on for further fractionation and compound isolation; SA 3, conduct bioassay-guided fractionation to isolate and identify compounds that act against these tropical diseases. These specific aims provide the focus for this International Research Scientist Development Award (IRSDA), involving U.S. and foreign mentors who have collaborated for years on the Panama ICBG, and who have in place a tremendous plan for the training and mentorship of the candidate.