NEW ANTITUMOR & ANTIFUNGAL NATURAL PRODUCTS FROM FUNGI

通过对微生物的研究，已经发现了许多有用的药物。 天然产品。 然而，有一些真菌亚群， 尚未广泛研究次级代谢产物的产生。 此外，许多物种的生态和生命周期的某些方面 这些真菌特别表明，它们应该成为 探索寻找新的具有生物活性的天然产物。 自然竞争真菌物种之间的拮抗作用一直是 许多文献报道的主题。 化合物负责这样的 效果基本上是天然的抗真菌剂，这也可能表现出 其他有用的生物活性。 其他真菌占据着独特的营养 环境，这表明它们可能具有代谢适应性， 与更常见的真菌不同。 另一类真菌产生大量的 一种叫做菌核的生理结构， 有大量证据表明，其中许多 菌核含有独特的生物活性次级代谢产物， 以食真菌昆虫为食。 我们的利益在于三个小组， 真菌表现出这样的特点：粪生，海洋/水生，和 核盘菌 我们认为这三种真菌 包括新天然产物的潜在有价值的来源， 药理活性 因此，我们打算进行研究， 这三种真菌亚群的次级代谢产物， 具有抗真菌、抗肿瘤、抗病毒和其它作用的新化合物， 潜在有用的生物活性。 我们的研究方法在很大程度上是非随机的，因为它是基于 应用文献证据、生态学原理， 分类学关系 真菌物种将被选择用于研究 基于对竞争对手的拮抗作用的文献报告， 在真菌演替中晚期出现，在海洋环境中出现， 菌核形成能力，以及与具有 在我们的初步研究中已经产生了生物活性剂。 新鲜 将获得真菌种的分离物和真菌菌核样品 通过与真菌学领域专家的合作安排， 和真菌分类学。 预筛选培养物、提取物， 色谱级分，和纯化的抗真菌代谢物， 抗生素，和潜在的抗肿瘤活性将在我们的 实验室，和一组25个额外的屏幕（抗肿瘤，抗病毒， 抗真菌、免疫调节等）将由一个合作的 制药公司。 最先进的色谱和 光谱技术将用于分离和结构 活性代谢物的测定。 初步结果表明， 到目前为止，我们选择的真菌中有10%产生的提取物， 表现出活动，我们已经分离和表征了20多个新的 生物活性的天然产品使用这种方法。 通过我们 在这方面的研究，我们建议探索天然产物化学 这些真菌亚群，同时评估的潜力， 生态为基础的方法来发现新的生物活性剂。

Many useful drugs have been discovered through studies of microbial natural products. However, there are a number of fungal subgroups that have not been widely studied for secondary metabolite production. Furthermore, certain aspects of the ecology and life-cycles of many of these fungi specifically suggest that they should be targeted for exploration in the search for new biologically active natural products. Antagonism between species of naturally-competing fungi has been the subject of numerous literature reports. Compounds responsible for such effects are essentially natural antifungal agents, which may also exhibit other useful bioactivities. Other fungi occupy unique nutritional environments, suggesting that they may possess metabolic adaptations that differ from more common fungi. Yet another group of fungi produce large physiological structures called sclerotia that are vital to the survival of the organism, and there is significant evidence that many of these sclerotia contain unique bioactive secondary metabolites that deter feeding by fungivorous insects. Our interests lie with three subgroups of fungi that exhibit such characteristics: coprophilous, marine/aquatic, and sclerotium-forum fungi. We propose that these three types of fungi comprise a potentially valuable source of new natural products with pharmacological activity. Therefore, we intend to undertake studies of the secondary metabolites of these three fungi subgroups in search of novel compounds with antifungal, antitumor, antiviral, and other potentially useful bioactivities. Our approach to this research is largely non-random, since it is based on the application of literature evidence, ecological rationale, and taxonomic relationships. Fungal species will be chosen for study on the basis of literature reports of antagonistic effects toward competitors, late occurrence in fungal successions, occurrence in marine environments, sclerotium-forming ability, and taxonomic relationship to fungi that have already yielded bioactive agents in our preliminary studies. Fresh isolates of fungi species and sample of fungi sclerotia will be obtained through collaborative arrangements with experts in the fields of mycology and fungal taxonomy. Prescreens of culture filtrates, extracts, chromatographic fractions, and purified metabolites for antifungal, antibiotic, and potential antitumor activities will be conducted in our laboratory, and a battery of 25 additional screens (antitumor, antiviral, antifungal, immunomodulatory, etc.) will be conducted by a cooperating pharmaceutical company. State-of-the art chromatographic and spectroscopic techniques will be used in the isolation and structure determination of active metabolites. Initial results indicate that a high percentage of the fungi we have selected thus far produce extracts that exhibit activity, and we have isolated and characterized over twenty new biologically active natural products using this approach. Through our studies in this area, we propose to explore the natural products chemistry of these fungi subgroups, while evaluating the potential of an ecologically-based approach to the discovery of novel bioactive agents.