CHEMICAL DIVERSITY LIBRARIES FROM MEDICINAL PLANTS (RMI)

药用植物化学多样性库 (RMI)

基本信息

批准号：
7274185
负责人：
KUO-HSIUNG LEE
金额：
$ 39.22万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-23 至 2009-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this proposed study is the generation of pilot-scale chemical diversity libraries, which will be used for high-throughput screening (HTS) by the Molecular Libraries Screening Center Network (MLSCN). The compounds included in these libraries will be derived from medicinal plants - both isolated natural products and synthetic modified derivatives. Naturally occurring compounds representing unique chemical diversity classes will be isolated, purified, and characterized using modern chemical, physical, and spectral techniques, including LC-MSn technology. Compounds will be obtained from three main sources: bioactive natural products previously investigated by the PI's Natural Product Laboratory (NPL) in the past 34 years, constituents of medicinal plants commonly used in the US, and constituents of medicinal plants commonly used outside of the US, particularly in traditional Chinese medicine (TCM). In addition, rational chemical synthetic modification of water-insoluble natural products will provide new water-soluble analogs that will be more amenable to HTS. Totally, more than 1,200 compounds over three years with 400 compounds per year will be submitted to the NIH Repository for HTS. All submitted compounds will be in greater than 99% purity and, initially, in 10 mg per compound quantity. Additional quantity of compounds with promising biological activity based on the initial HTS might be furnished, upon request. An in-house database will store information (source, structure, production and characterization methods, etc.) on all compounds and will be made available as part of the resource-sharing plan. No intellectual property claims are anticipated on submitted compounds. The compounds chosen for study will have high potential for in vivo and/or in vitro biological activity based on the history of folkloric and clinical medicinal use of the source plants. In addition, the constituents of these plant species will cover a wide range of unique chemical diversity space and, accordingly, be likely to affect the functions of novel classes of biomacromolecules. The expertise and productivity of the PI's NPL will assure the successful generation of chemical diversity libraries that have excellent promise to generate new scientific knowledge with tangible benefits for public health in the areas of new drug discovery and development.

描述（由申请人提供）：这项拟议的研究的总体目标是生成试验性化学多样性库，该库将用于分子库筛选中心网络（MLSCN）的高通量筛选（HTS）。这些文库中包含的化合物将来自药用植物 - 孤立的天然产物和合成修饰的衍生物。使用现代化学，物理和光谱技术（包括LC-MSN技术）的自然发生的代表独特化学多样性类别的自然化合物将被隔离，纯化和表征。化合物将从三个主要来源获得：PI的天然产品实验室（NPL）先前研究的生物活性天然产物（NPL）在过去的34年中，美国常用的药用植物的组成部分以及美国以外使用的药用植物的组成部分，尤其是在传统中药（TCM）中。此外，水不溶的天然产物的合理化学合成修饰将提供新的水溶性类似物，这将更适合HTS。总的来说，三年内有1,200多种化合物每年将提交HTS的NIH存储库。所有提交的化合物的纯度大于99％，最初为10 mg，每个化合物数量10 mg。可以根据要求提供基于初始HTS的有前途的生物活性的额外数量的化合物。内部数据库将在所有化合物上存储信息（源，结构，生产和表征方法等），并将作为资源共享计划的一部分提供。预计提交的化合物不会提出知识产权索赔。根据民俗和/或体外生物学活性，基于民俗和临床药物的使用史，选择用于研究的化合物将具有很高的体内和/或体外生物学活性的潜力。此外，这些植物物种的成分将涵盖广泛的独特化学多样性空间，因此，可能会影响新型生物乳清分子的功能。 PI的NPL的专业知识和生产力将确保成功产生化学多样性库，这些图书馆具有极好的希望，可以在新药发现和开发领域产生新的科学知识，并为公共卫生带来明显的收益。