Core--Plant Natural Products

这一核心项目的目标是(1)工厂材料的选择和采购 具有潜在的致癌抑制活性；(2)发现新的天然产物 化学致癌的抑制剂。植物材料的选择将集中于三大类：(A)可食用植物，主要是非美国植物；(B)传统医药系统中使用的药用植物，特别是那些用于癌症相关治疗的植物；以及(C)据报道在与癌症化学预防有关的化验中具有活性，但未经化学研究的特有植物，特别是那些没有毒性历史，并有可能产生新化合物的植物。 主要重点将放在(A)和(B)类植物上。这些候选植物将是 在我们的合作者的帮助下被认同。最有希望的植物品种将被选为 在对文献进行分析的基础上进行收购。无毒的植物材料将被优先收集。候选植物材料将在田间采集、栽培和/或以商业方式购买。所有植物材料都将经过鉴定和认证。它们将被干燥、碾磨和提取以进行生物检测。这些材料(1-10公斤批次)将被提取并 通过生物测定指导有效成分的分离。最初的生物测定导向分离将集中在非极性提取物上。活性提取物将通过最合适的层析方法进行分离纯化。将使用包括LC/MS/MS(项目4)和X射线结晶学方法在内的物理和化学方法来确定活性成分的结构，这些活性成分将作为新的先导化合物用于后续的合成研究，并接受进一步的体内化学致癌抑制效果、机制和临床前的评价。

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.