Core--Plant Natural Products

本核心项目的目标是（1）植物材料的选择和采购 具有潜在的致癌抑制活性和（2）发现新的天然产物 化学致癌抑制剂。植物材料的选择将集中在三个主要类别：（a）食用植物，主要是非美国;（B）用于传统医学系统的药用植物，如传统中药，特别是用于癌症相关治疗的植物;和（c）据报道在与癌症化学预防有关的测定中具有活性，但尚未进行化学研究的特有植物，特别是那些没有毒性史并具有产生新化合物的潜力的化合物。 主要重点将放在（a）和（B）组植物上。这些候选植物将是 在我们的合作者的帮助下确定。最有前途的植物物种将被选中， 在分析文献的基础上，无毒植物材料将优先收集。候选植物材料将在田间收集、栽培和/或商业购买。所有工厂材料都将被识别和认证。将其干燥、研磨并提取用于生物测定。将浸提这些材料（1-10 kg批次）， 进行活性成分的生物测定定向分离。最初的生物测定定向分离将侧重于非极性浸提液。将通过最适当的色谱方法分离和纯化活性提取物。将使用物理和化学方法，包括LC/MS/MS（项目4）和X射线晶体学方法来确定活性成分的结构，这些活性成分将作为后续合成研究的新先导化合物，并进行进一步的体内化学致癌抑制功效、机理和临床前评价。

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.