It is proposed to continue to search for novel natural product inhibitors of chemical carcinogenesis of natural origin from plant sources, using bioactively-guided fractionation techniques. Non-polar and polar extracts of species chosen for study in this investigation will be prepared and submitted to in vitro and in vivo biological evaluations. Those extracts selected for bioassay-directed fractionation on the basis of activity will be chromatographed according to well-established phytochemical procedures, with the fractions so obtained being monitored by the short-term in vitro bioassay in which the greatest activity was originally demonstrated. Spectroscopic and chemical methods will be used to determine the structures of pure bioactive compounds. In concert with literature management studies being performed elsewhere in this investigation, efforts will be made to minimize the re-isolation of compounds with known chemopreventive activity. When deemed appropriate by group decision of the senior personnel associated with this Program Project, large-scale isolation of active compounds will be undertaken from 5-50 kg quantities of plant material, in order to obtain gram quantities of particularly promising substances. Thus, it is expected that this project will continue to provide new chemical entities with cancer inhibitory activity for detailed evaluation. Such naturally occurring compounds might have mechanistic or even clinical value per se, or alternatively might serve as new lead compounds for subsequent synthetic modification in this Program Project.
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