CHEMICAL DIVERSITY LIBRARIES FROM MEDICINAL PLANTS

描述（由申请方提供）：本拟议研究的总体目标是生成中试规模的化学多样性文库，该文库将用于分子文库筛选中心网络（MLSCN）的高通量筛选（HTS）。这些库中包含的化合物将来自药用植物-分离的天然产物和合成的修饰衍生物。代表独特化学多样性类别的天然化合物将使用现代化学，物理和光谱技术（包括LC-MSn技术）进行分离，纯化和表征。化合物将从三个主要来源获得：PI天然产物实验室（NPL）在过去34年中研究的生物活性天然产物，美国常用的药用植物成分，以及美国以外常用的药用植物成分，特别是传统中药（TCM）。此外，对水不溶性天然产物进行合理的化学合成修饰将提供新的水溶性类似物，这些类似物将更适合HTS。总共有超过1，200种化合物在三年内，每年400种化合物将提交给NIH HTS储存库。所有提交的化合物的纯度将大于99%，最初，每种化合物的量为10 mg。根据要求，可以提供基于初始HTS具有有希望的生物活性的额外量的化合物。内部数据库将存储信息（来源、结构、生产和表征方法等）所有营地都将得到这一信息，并将作为资源共享计划的一部分提供。预计不会对提交的化合物提出知识产权要求。根据来源植物的民俗和临床药用历史，选择用于研究的化合物将具有体内和/或体外生物活性的高潜力。此外，这些植物物种的成分将涵盖广泛的独特的化学多样性空间，因此，可能会影响新类别的生物大分子的功能。PI的NPL的专业知识和生产力将确保成功生成化学多样性库，这些库具有很好的前景，可以产生新的科学知识，为新药发现和开发领域的公共卫生带来切实利益。

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.