BIOCHEMISTRY AND FUNCTION OF MARCOCYCLIC POLYAMINE ALKALOIDS

大环多胺生物碱的生物化学和功能

• 批准号: 6107366
• 负责人: BARBARA MEURER-GRIMES
• 金额: --
• 依托单位: HERBERT H. LEHMAN COLLEGE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107366
• 关键词: Cruciferae; alkaloids; antibacterial agents; antifungal agents; antiviral agents; bioassay; chemical structure function; cytotoxicity; growth inhibitors; mass spectrometry; nuclear magnetic resonance spectroscopy; plant extracts; polyamines; thin layer chromatography

The long-term objective of this application is to characterize the chemical structures and biological activity of macrocyclic polyamine alkaloids and their precursors. These substances have been reported to exhibit antibacterial, antifungal, and antiviral activity and therefore are promising targets for the development of novel plant derived medicines. These studies are important because they will identify compounds that may successfully be used in home health care products, against a multitude of human pathogens and diseases, and possibly for the treatment of opportunistic infections that commonly occur in patients with any kind of immunosuppression. To date over 50 macrocyclic polyamine alkaloids have been described from plants, particularly of the families Celastraceae, Acanthaceae, Scrophulariaceae, Brassicaceae, a few other plant families, and several bacteria. The count does not include their synthetic analogues and numerous biological precursors. Many of these compounds have been successfully synthesized in the laboratory, which increases their potential for commercial development. The chemical structures of these substances are often based on the biogenic amines putrescine, spermidine and spermine that, in most cases are substituted with cinnamic acids to form complex macrocyclic structures. In continuation of our research program on cinnamic acid amides, we propose to elucidate the structures and test the biodynamic activity of polyamine derived alkaloids obtained from: a) greenhouse cultivated species of Lunaria and Verbascum, b) ethnobotanical plant collections of Celastraceae, Acanthaceae, and Scrophulariaceae. The ethnobotanical plant collections will be obtained in collaboration with consultants at the New York Botanical Garden. The substances will be isolated from the plant material by bioassay directed fractionation. The biological activity will be determined on cultures of several bacteria, and one fungus, and BKH cells. Quantitative assays are planned to determine the minimum inhibitory concentration (MIC) of the pure compounds. Cytotoxicity and antiviral activity of selected isolates will be determined at the Albert Einstein College of Medicine. Novel compounds will elucidated by spectroscopic methods. This research project is a joint, interdisciplinary effort by MBRS students and prime research institutions located in the Bronx including The City University of New York (Lehman College campus), The New York Botanical Garden, and the Albert Einstein College of Medicine.

该应用的长期目标是表征 大环多胺的化学结构和生物学活性 生物碱及其前体。 据报道这些物质 表现出抗菌，抗真菌和抗病毒活性，因此 是开发新植物的有希望的目标 药物。 这些研究很重要，因为它们会确定 可以成功用于家庭保健产品的化合物， 针对多种人类病原体和疾病，可能是针对 在患者中通常发生的机会性感染的治疗 任何一种免疫抑制。 迄今为止超过50个大环的多胺 生物碱已从植物，特别是家庭中描述 celastraceae，acanthaceae，scrophariaceae，brassicaceae，其他一些 植物科和几种细菌。 计数不包括他们的 合成类似物和许多生物学前体。 其中许多 化合物已在实验室中成功合成，该化合物已 增加了他们的商业发展潜力。 化学物质 这些物质的结构通常基于生物胺 在大多数情况下，腐烂，精子和精子可以取代 与肉桂酸形成复杂的大环结构。 在 我们提出的关于肉桂酸酰胺的研究计划的延续，我们建议 阐明结构并测试多胺的生物动力活性 衍生的生物碱从：a）温室栽培物种 Lunaria和Verbascum，b）民族植物植物收集 celastraceae，acanthaceae和scrophariaceae。 民族植物植物 收款将与新的顾问合作获得 约克植物园。 物质将与植物隔离 生物测定的材料定向分馏。 生物活性将 确定几种细菌，一种真菌和BKH的培养物 细胞。 计划定量测定以确定最低 纯化合物的抑制浓度（MIC）。 细胞毒性和 选定分离株的抗病毒活性将在阿尔伯特确定 爱因斯坦医学院。 新颖的化合物将通过 光谱法。 该研究项目是一个联合 MBRS学生和主要研究机构的跨学科努力 位于布朗克斯 大学校园），纽约植物园和阿尔伯特·爱因斯坦 医学院。