The overall goal of this program proposal is to discover naturally occurring anticancer lead compounds thatwill be more effective than currently available cancer chemotherapeutic agents. Project 2, at the College ofPharmacy, UIC is comprised of botanical, chemical and biological elements.
The specific aims for Project 2are 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, producing200 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 showingantineoplastic activity will be fractionated using bioguided fractionation protocols to obtain pure naturalproduct(s). We will use microcoil NMR and LC-MS methods to determine the structures of the pure activecompounds; these sensitive analytical techniques reduce the amount of pure material needed for structureelucidation to 10-50ug and thus speed up the isolation and structure determination process. Structurallycharacterized active isolates will be submitted for more extensive evaluation in biological test systemsavailable at Cores A and C and Projects 1 and 3 as well as chemical optimization (Core B). We will re-isolatelarger amounts of any promising candidate compounds for further evaluation. 3) To acquire all plantmaterials that will be required by the proposed Program Project, inclusive of 300 new and fully documentedplant samples for extraction and initial biological evaluation per year, as well as re-collected plant materialsfor 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 structuredetermination of minor active metabolites using microcoil NMR.This will enable all projects to performstructure determination on 10-50 ug of active isolates.Relevance of Research to Public HealthThe primary purposes of this part of the program project are to discover new cancer chemotherapeuticagents from cyanobacteria and to supply plants from tropical rainforests for investigation. This will be done ina coordinated manner with the other technical and administrative components of this project.
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