Core--Plant Natural Products

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The objectives of this core project are (1) the selection and procurement of plant materials having potential carcinogenesis inhibitory activity and (2) the discovery of novel natural products inhibitors of chemical carcinogenesis. Selection of plant materials for study will be focused on three major groups: (a) edible plants, primarily non-USA; (b) medicinal plants used in traditional systems of medicine such as Traditional Chinese Medicine, particularly those employed in cancer related therapies; and (c) endemic plants reported to have activity in an assay pertinent to cancer chemoprevention, but which have not been investigated chemically, especially those with no history of toxicity, and having potentials to yield novel chemical compounds. Primary emphasis will be placed on group (a) and (b) plants. These candidate plants will be identified with help from our collaborators. Most promising plant species will be selected for acquisition based on analysis of the literature. The non-toxic plant materials will be given a higher priority for collection. The candidate plant materials will be field collected, cultivated and/or commercially purchased. All plant materials will be identified and authenticated. They will be dried, milled, and extracted for bioassay. These materials (1-10 kg lots) will be extracted and subjected to bioassay-directed isolation of the active principles. The initial bioassay-directed isolation will focus on the non-polar extracts. The active extracts will be separated and purified by the most appropriate chromatographic methods. Physical and chemical methods, including LC/MS/MS (Project 4) and X-ray crystallographic methods will be used to determine the structures of the active constituents, which will serve as new lead compounds for subsequent synthetic studies, and be subjected to further in vivo inhibitory efficacy of chemical carcinogenesis, mechanistic and preclinical evaluations.