ANTINEOPLASTIC AGENTS FROM MARINE BACTERIA

来自海洋细菌的抗肿瘤剂

• 批准号: 3460531
• 负责人: BRADLEY S DAVIDSON
• 金额: $ 8.79万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-05 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3460531
• 关键词: antineoplastics; bioassay; biological products; chemical structure function; cytotoxicity; drug screening /evaluation; microorganism mass culture; nuclear magnetic resonance spectroscopy; saltwater environment

DESCRIPTION (Investigator's Abstract): Recent studies have demonstrated that marine bacteria, likely their terrestrial counterparts, may be a prolific source of unique compounds. To date, even though both shallow water and deep marine habitats have been shown to contain a taxonomically diverse array of microorganisms, the investigation of these microorganisms has largely been ignored by natural products chemists. Marine bacteria have the potential to provide a virtually untapped source of new chemotherapeutic agents. The goal of the proposed research project is the discovery of new antineoplastic agents from bacteria isolated from the marine environment. Bacteria will be isolated from both shallow and deep ocean sediments, as well as shallow sea water. To maximize the detection of pharmaceutically relevant compounds, extracts of liquid bacterial cultures will initially be assayed for biological activity using antimicrobial, antiviral, DNA-binding , and solid tumor cytotoxicity assays. Those culture whose extracts exhibit promising activity will be scaled-up to obtain extracts for the isolation and structure identification of the active compounds. The chemical structures of the biologically active secondary metabolites will be deduced through both chemical and spectroscopic methods, and, in particular, through the application of new and unique one- and two-dimensional NMR techniques.Purified cytotoxic compounds will then be subjected to further analysis to gain insight into the mechanism of action, and whether the cytotoxicity of a given compound is the result of inhibition of topoisomerase II.

描述（研究者摘要）：最近的研究表明 海洋细菌，很可能是它们的陆地细菌，可能是 独特化合物的丰富来源。 迄今为止，尽管两者都很浅 水和深海生境已被证明包含分类学上的 多种微生物，对这些微生物的研究 很大程度上被天然产物化学家所忽视。 海洋细菌 有潜力提供几乎未开发的新资源 化疗剂。 拟议研究项目的目标是 从分离的细菌中发现新的抗肿瘤药物 海洋环境。 细菌将被从浅层和深层隔离 海洋沉积物以及浅海水。 最大化检测 药学相关化合物、液体细菌提取物 最初将使用以下方法测定培养物的生物活性 抗菌、抗病毒、DNA 结合和实体瘤细胞毒性 化验。 那些提取物表现出有希望活性的培养物将被 放大以获得提取物用于分离和结构鉴定 的活性化合物。 生物化学结构 活性次生代谢物将通过化学和 光谱方法，特别是通过应用新的 和独特的一维和二维核磁共振技术。纯化的细胞毒性 然后对化合物进行进一步分析以深入了解 作用机制以及给定化合物是否具有细胞毒性 是拓扑异构酶 II 抑制的结果。