The major objectives of Program 2 of this overall research program are to prepare extracts of all collected plant materials for initial biological testing and to isolate and structurally characterize novel antineoplastic agents from plants. Species collected in the field will be received by Program 1, and a non-polar (organic solvent-soluble) and a polar (aqueous-soluble) extract will be prepared for each sample. Each non-polar extract will be distributed to Programs 3, 4, and 5 for initial biological evaluation while the aqueous extracts will be stored in a frozen repository in case of later need. Dereplication of known active compounds will be performed by HPLC/MS, coupled with a consideration of prior chemotaxonomic literature. The active principle(s) of each recollected, satisfactorily dereplicated, confirmed-active plant part made available by Program 1 will be isolated by a combination of standard solvent partition and chromatographic procedures, using one of the various bioassays that have been developed by the consortium to guide the fractionation. Spectroscopic and chemical methods will be used to determine the structures of each pure active isolate. Particular emphasis will be given to modern one- and two dimensional nuclear magnetic resonance techniques for compound structure elucidation. To permit more advanced biological testing to be performed and also to aid in analog development studies, active compounds will bed re-isolated in larger quantities, when deemed appropriate by the consortial group. It is anticipated that the overall outcome of Program 2 will be the discovery of one or more selectively active natural products that show promise for future development as cancer chemotherapeutic agents.
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