Cultured Cyanobacteria, Isolation Chemistry, Structure Elucudation, and Plant Acq

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The overall goal of this program proposal is to discover naturally occurring anticancer lead compounds that will be more effective than currently available cancer chemotherapeutic agents. Project 2, at the College of Pharmacy, UIC is comprised of botanical, chemical and biological elements. The specific aims for Project 2 are as follows: 1) To obtain, culture, and prepare extracts of cyanobacterial strains. We will obtain, culture, and extract 100 cyanobacterial strains a year. Each strain will be cultured in two different media, producing 200 cyanobacterial samples for biological evaluation in Projects 1 (OSU), 3 (RTI)and Cores A (UIC) and C (B-MS). 2) To isolate and determine the structures of the active cyanobacterial metabolites. Extracts showing antineoplastic activity will be fractionated using bioguided fractionation protocols to obtain pure natural product(s). We will use microcoil NMR and LC-MS methods to determine the structures of the pure active compounds; these sensitive analytical techniques reduce the amount of pure material needed for structure elucidation to 10-50ug and thus speed up the isolation and structure determination process. Structurally characterized active isolates will be submitted for more extensive evaluation in biological test systems available at Cores A and C and Projects 1 and 3 as well as chemical optimization (Core B). We will re-isolate larger amounts of any promising candidate compounds for further evaluation. 3) To acquire all plant materials that will be required by the proposed Program Project, inclusive of 300 new and fully documented plant samples for extraction and initial biological evaluation per year, as well as re-collected plant materials for larger scale isolation leading to more detailed biological evaluation as needed. In addition, the UIC project will provide analytical support for Projects 1 (OSU)and 3 (RTI)in the structure determination of minor active metabolites using microcoil NMR.This will enable all projects to perform structure determination on 10-50 ug of active isolates. Relevance of Research to Public Health The primary purposes of this part of the program project are to discover new cancer chemotherapeutic agents from cyanobacteria and to supply plants from tropical rainforests for investigation. This will be done in a coordinated manner with the other technical and administrative components of this project.