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: 8325896
• 负责人: JIMMY ORJALA
• 金额: $ 51.94万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325896
• 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.

这项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，麻省理工学院 药学，UIC由植物、化学和生物元素组成。项目2的具体目标 主要内容如下：1)蓝藻菌株提取液的获取、培养和制备。我们将获得，文化， 每年提取100个蓝藻菌株。每个菌株将在两种不同的培养基中培养，产生 项目1(OSU)、项目3(RTI)和岩芯A(UIC)和C中用于生物评估的200个蓝藻样本 (B-MS)。2)分离和鉴定活性蓝藻代谢产物的结构。摘录显示 抗肿瘤活性将使用生物导向分级方案进行分级，以获得纯天然的 产品(S)。我们将使用微线圈核磁共振和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10-50微克，从而加快分离和结构确定过程。从结构上讲 将在生物测试系统中提交具有特征的活性分离株进行更广泛的评估 在核心A和C以及项目1和3以及化学优化(核心B)提供。我们将重新隔离 任何有希望的候选化合物的数量更多，以供进一步评估。3)收购所有工厂 提议的计划项目所需的材料，包括300份新材料和完整记录的材料 每年用于提取和初步生物评估的植物样本，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)和项目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微克活性菌株的结构测定。 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方法。 从蓝藻中提取药剂，并从热带雨林中提供植物进行调查。这将在#年完成。 与该项目的其他技术和行政部分协调一致。