Cultured Cyanobacteria, Isolation Chemistry, Structure Elucudation, and Plant Acq

培养蓝藻、分离化学、结构解析和植物采集

• 批准号: 7921382
• 负责人: JIMMY ORJALA
• 金额: $ 39.52万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7921382
• 关键词: Antineoplastic Agents; Applications Grants; Biological; Biological Factors; Biological Testing; Botanicals; Chemicals; Chemistry; Chicago; Collection; Country; Cyanobacterium; Elements; Evaluation; Fractionation; Geographic Locations; Goals; Habitats; Illinois; In Vitro; Individual; Institutes; Investigation; Lead; Malignant Neoplasms; Methods; Minor; Pharmacy facility; Phytochemical; Plants; Process; Protocols documentation; Public Health; Research; Sampling; Source; Speed; Structure; System; Techniques; Universities; Weight; chemotherapeutic agent; college; experience; novel; programs

The overall goal of this program proposal is to discover naturally occurring anticancer lead compounds that will be more effective than currently available cancer chemotherapeutic agents. Project 2, at the College of Pharmacy, UIC is comprised of botanical, chemical and biological elements. The specific aims for Project 2 are as follows: 1) To obtain, culture, and prepare extracts of cyanobacterial strains. We will obtain, culture, and extract 100 cyanobacterial strains a year. Each strain will be cultured in two different media, producing 200 cyanobacterial samples for biological evaluation in Projects 1 (OSU), 3 (RTI)and Cores A (UIC) and C (B-MS). 2) To isolate and determine the structures of the active cyanobacterial metabolites. Extracts showing antineoplastic activity will be fractionated using bioguided fractionation protocols to obtain pure natural product(s). We will use microcoil NMR and LC-MS methods to determine the structures of the pure active compounds; these sensitive analytical techniques reduce the amount of pure material needed for structure elucidation to 10-50ug and thus speed up the isolation and structure determination process. Structurally characterized active isolates will be submitted for more extensive evaluation in biological test systems available at Cores A and C and Projects 1 and 3 as well as chemical optimization (Core B). We will re-isolate larger amounts of any promising candidate compounds for further evaluation. 3) To acquire all plant materials that will be required by the proposed Program Project, inclusive of 300 new and fully documented plant samples for extraction and initial biological evaluation per year, as well as re-collected plant materials for larger scale isolation leading to more detailed biological evaluation as needed. In addition, the UIC project will provide analytical support for Projects 1 (OSU)and 3 (RTI)in the structure determination of minor active metabolites using microcoil NMR.This will enable all projects to perform structure determination on 10-50 ug of active isolates. Relevance of Research to Public Health The primary purposes of this part of the program project are to discover new cancer chemotherapeutic agents from cyanobacteria and to supply plants from tropical rainforests for investigation. This will be done in a coordinated manner with the other technical and administrative components of this project.

该计划提案的总体目标是发现天然存在的抗癌先导化合物 将比目前可用的癌症化疗药物更有效。项目2，在学院 UIC的药学由植物、化学和生物元素组成。项目2的具体目标 具体如下： 1)蓝藻菌株的获取、培养和提取物的制备。我们将获得，文化， 每年提取100株蓝藻。每个菌株将在两种不同的培养基中培养，产生 200 个蓝藻样本用于项目 1 (OSU)、3 (RTI) 以及核心 A (UIC) 和 C 中的生物学评估 (B-MS)。 2）分离并确定蓝藻活性代谢物的结构。摘录显示 抗肿瘤活性将使用生物引导分馏方案进行分馏以获得纯天然 产品）。我们将使用微线圈 NMR 和 LC-MS 方法来确定纯活性物质的结构 化合物；这些灵敏的分析技术减少了结构所需的纯材料的数量 澄清至10-50ug，从而加速分离和结构测定过程。结构上 将提交特征活性分离物以在生物测试系统中进行更广泛的评估 可在核心 A 和 C、项目 1 和 3 以及化学优化（核心 B）中使用。我们将重新隔离 大量任何有希望的候选化合物以进行进一步评估。 3) 收购所有工厂 拟议计划项目所需的材料，包括 300 份新的且完整记录的材料 每年用于提取和初步生物学评估的植物样品，以及重新收集的植物材料 用于更大规模的分离，从而根据需要进行更详细的生物学评估。 此外，UIC项目将为结构中的项目1（OSU）和3（RTI）提供分析支持 使用微线圈 NMR 测定次要活性代谢物。这将使所有项目能够执行 10-50 ug 活性分离物的结构测定。 研究与公共卫生的相关性 这部分计划项目的主要目的是发现新的癌症化疗药物 蓝细菌制剂并提供来自热带雨林的植物进行研究。这将在 与该项目的其他技术和管理部分进行协调。