NEW BIOACTIVE NATURAL PRODUCTS FROM FRESHWATER FUNGI

来自淡水真菌的新型生物活性天然产品

• 批准号: 6039025
• 负责人: JAMES B GLOER
• 金额: $ 32.34万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6039025
• 关键词: Fungi; antifungal agents; aquatic organism; drug discovery /isolation; fresh water environment; high performance liquid chromatography; microorganism culture; plant extracts; spectrometry

This application requests support for an investigation of the natural products chemistry of freshwater filamentous fungi. These rarely-studied fungi are ecologically, morphologically, and taxonomically distinctive, and they commonly display antagonistic effects against other fungi. Like our previous and productive chemical studies of sclerotial and coprophilous fungi, this investigation will employ a systematic, ecology-based approach to organism selection that represents a departure from traditional random microbial screening programs. Based on the propensity of these fungi to show antagonistic effects toward other fungi, together with the increasingly urgent need for new treatments to fight opportunistic fungal infections in humans, efforts will focus on a search for new metabolites with antifungal effects. However, pure compounds will also be tested for other activities through arrangements with a major pharmaceutical company, and by submission to the NCI's antitumor screens. The proposed work involves a collaboration between the PI's group and that of Prof. Carol Shearer, one of the world's foremost experts in aquatic mycology. Preliminary studies of selected aquatic isolates have already afforded 37 new bioactive agents, including some with unusual structures. These initial results provide evidence that this unique, virtually unexplored group of fungi shows considerable promise as a source of novel bioactive natural products, and clearly demonstrate the ability of the research team to perform the proposed studies. Many isolates that exhibit antifungal effects in direct competition assays are available for immediate investigation, and there are no literature reports of prior chemical studies of any of these organisms. Fungal isolates will be cultivated under both liquid and solid-substrate growth conditions, and extracts from these cultures will be subjected to antifungal assays to prioritize cultures for chemical study. Active components will be isolated through bioassay-guided fractionation, and their structures will be determined using spectroscopic methods. While chemical studies progress, further freshwater species will be isolated, identified, and screened for antifungal activity, thereby providing a continuing stream of new isolates for investigation.

本申请请求支持淡水丝状真菌天然产物化学的研究。这些很少被研究的真菌在生态学、形态学和分类学上都是独特的，它们通常对其他真菌表现出拮抗作用。 就像我们以前对菌核和粪生真菌进行的富有成效的化学研究一样，这项调查将采用一种系统的、基于生态学的方法来进行生物体选择，这代表了对传统随机微生物筛选程序的背离。 基于这些真菌对其他真菌表现出拮抗作用的倾向，以及对新治疗方法的日益迫切的需求，以对抗人类机会性真菌感染，努力将集中在寻找具有抗真菌作用的新代谢物上。然而，纯化合物也将通过与一家大型制药公司的安排进行其他活性测试，并提交给NCI的抗肿瘤筛选。 拟议的工作涉及PI小组与世界上最重要的水生真菌学专家之一Carol Shearer教授的合作。 对选定的水生分离物的初步研究已经提供了37种新的生物活性剂，包括一些具有不寻常结构的生物活性剂。 这些初步结果提供了证据，表明这种独特的，几乎未被探索的真菌群作为新型生物活性天然产物的来源显示出相当大的前景，并清楚地表明研究团队有能力进行拟议的研究。 许多在直接竞争试验中表现出抗真菌作用的分离株可用于立即调查，并且没有任何这些生物体的先前化学研究的文献报告。 将在液体和固体基质生长条件下培养真菌分离株，并对这些培养物的提取物进行抗真菌试验，以确定用于化学研究的培养物的优先顺序。 活性成分将通过生物测定指导的分馏分离，并使用光谱方法确定其结构。 随着化学研究的进展，将进一步分离、鉴定和筛选淡水物种的抗真菌活性，从而为研究提供源源不断的新分离株。