ISOLATION AND STRUCTURE DETERMINATION OF CYANOBACTERIAL ANTITUMOR AGENTS

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This Laboratory Program will provide natural product samples for the NCNPDDG. A total of 1,000 blue-green algae (cyanobacteria) will be extracted each year with both a lipophilic and a hydrophilic solvent system. These extracts will be submitted to Wayne State University for analysis. Extracts which exhibit solid tumor and/or tumor selective activity will be fractionated so that the active compound can be purified and identified. Highest priority will be given to those extracts that are active against drug-resistant solid tumors. We expect that about 0.5% of the extracts will demonstrate activity worth pursuing. Scale-up batches will then be pursued to provide sufficient material for in vivo testing. The identified active component will initiate an analog synthesis program as well as a search through the inventories of both Eli Lilly and NCI for analogs to test. Approximately 1 purified compound per year is expected to begin pharmacological studies as well as mechanism of action studies.