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，可能是它们的陆地对应物， 独特化合物的丰富来源。 到目前为止，尽管双方都很肤浅， 水和深海栖息地已被证明包含一个分类 各种各样的微生物，对这些微生物的研究 在很大程度上被天然产物化学家所忽视。 海洋细菌 有潜力提供一个几乎未开发的新资源， 化疗剂。 拟议研究项目的目标是 发现新的病原体的细菌分离自 海洋环境 细菌将从浅层和深层分离出来 海洋沉积物以及浅海水。 为了最大限度地探测 药物相关化合物、液体细菌提取物 培养物最初将使用 抗微生物、抗病毒、DNA结合和实体瘤细胞毒性 测定。 其提取物表现出有希望的活性的那些培养物将是 放大以获得用于分离和结构鉴定的提取物 的活性化合物。 化学结构的生物 活性次级代谢产物将通过化学和 光谱方法，特别是通过应用新的 以及独特的一维和二维NMR技术。 然后将对化合物进行进一步分析，以了解 作用机制，以及给定化合物的细胞毒性是否 是抑制拓扑异构酶II的结果。