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

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.

这个项目的总体目标是发现新的天然产品与抗癌应用从海洋蓝藻和藻类使用基于机制的分析对表观遗传目标。热带浅水底栖蓝藻和藻类是生产与医学相关的天然产品的丰富分类群。然而，在以前的抗癌药物发现项目中，大多数海洋蓝藻和许多大型藻类的样本很少，很大程度上被忽视了，主要是因为大多数物种在自然条件下获得的生物量很少。在这项拟议的工作中，一个重要和潜在的假设正在被检验，即属于许多属的海洋蓝藻，而不是那些迄今为止研究过的，也将在生产抗癌型天然产品方面丰富。