New Approaches to Anticancer Agents from Cyanobacteria

蓝藻抗癌剂的新方法

• 批准号: 6924485
• 负责人: William Henry Gerwick
• 金额: $ 27.12万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6924485
• 关键词: Cyanophyta; algae; antineoplastics; aquatic organism; biological products; biotechnology; cooperative study; drug discovery /isolation; high performance liquid chromatography; liquid chromatography mass spectrometry; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; saltwater environment; Cyanophyta; algae; antineoplastics; aquatic organism; biological products; biotechnology; cooperative study; drug discovery /isolation; high performance liquid chromatography; liquid chromatography mass spectrometry; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; saltwater environment

The overarching goal of this project is to discover new natural products with anticancer applications from marine cyanobacteria and algae using mechanism-based assays against epigenetic targets. Tropical shallow water benthic cyanobacteria and algae have been rich taxonomic groups for the production of medicinally-relevant natural products. However, the majority of the ocean's cyanobacteria and many macroalgae have been little sampled and largely overlooked in previous anticancer drug discovery programs, mainly because most species attain little biomass under natural conditions. One important and underlying hypothesis being examined in this proposed work is that marine cyanobacteria belonging to many genera other than those studied to date will also be rich in their production of anticancer-type natural products. The specific aims which lead to this long term goal are: 1. To access previously unstudied marine cyanobacteria and macroalgae through examination of new habitats and new strategies for their collection and culture 2. To apply improved and innovative paradigms to enhance the detection of bioactive compounds from cyanobacterial/macroalgal extracts, including prefractionation and pure compound library formation 3. To screen marine cyanobacterial and algal derived compounds and reduced complexity mixtures for anticancer-type activities at Novartis (NIBR) using contemporary mechanism-based screening against epigenetic targets 4. To derepticate nuisance compounds through application of combined LC-MS and Microcoil NMR profiling procedures 5. To isolate and structurally define cyanobacterial and algal metabolites that are active in the NIBR mechanism-based assays using HPLC followed by efficient NMR and MS methodologies 6. To scale-up the isolation of active compounds to assist NIBR drug development efforts using recollection, culture, genetic-based methods, or synthetic/semi-synthetic methods, as appropriate and efficient 7. To patent notable discoveries and publish all results in the peer-reviewed literature.

该项目的总体目标是使用基于机制的表观遗传靶标的抗癌药物发现新的天然产品。热带浅水底栖蓝细菌和藻类已经是与药物相关的天然产物生产的丰富分类组。但是，在以前的抗癌药物发现计划中，大多数海洋的蓝细菌和许多大藻类都没有被采样，并且在很大程度上被忽略了，这主要是因为大多数物种在自然条件下几乎没有生物质。在这项拟议的工作中检查了一个重要的和基本的假设是，除了迄今为止研究的属属属外，属于许多属的海洋蓝细菌也将在其抗癌型天然产物的产生中富裕。 导致这个长期目标的具体目的是：1。通过检查新栖息地和新的栖息地以及其收藏和文化2的新策略，以获取先前未研究的海洋蓝细菌和大藻类。使用现代机制筛查表观遗传靶标的蓝细菌和藻类衍生化合物和抗癌型活性的复杂性混合物的降低的复杂性混合物 4。通过应用合并的LC-MS和微层NMR分析程序来表达滋扰化合物。5。隔离和结构定义氰基菌群和藻类代谢物，在基于NIBR机制的基于NIBR机制的测定中使用HPLC进行基于NMR和MS方法的缩放量的NIBRED STAIBRECTIOS 6。方法或合成/半合成方法，适当有效地7。专利发现并在同行评审的文献中发布所有结果。