ANTICANCER AGENTS FROM CYANOPHYTES AND MARINE ORGANISMS

来自蓝藻和海洋生物的抗癌剂

• 批准号: 3163672
• 负责人: RICHARD E MOORE
• 金额: $ 21.31万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-08-01 至 1994-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163672
• 关键词: Cnidaria; Cyanophyta; Epstein Barr virus; Invertebrata; Pacific Islands; Porifera; alternatives to animals in research; animal extract; antineoplastics; bioassay; biological products; chemical carcinogenesis; chemical structure; cytotoxicity; drug design /synthesis /production; drug metabolism; drug screening /evaluation; gel electrophoresis; microorganism culture; nasopharynx; nuclear magnetic resonance spectroscopy; oral pharyngeal neoplasm; physical separation; saltwater environment; stereochemistry; thin layer chromatography; tissue /cell culture

The main goal of this research is to discover new natural products from blue-green algae (cyanobacteria) and marine animals possessing algal symbionts that will be useful as drugs in the treatment of cancer or its prevention and/or as pharmacological tools for the study of chemical carcinogenesis. Ne isolates of blue-green algae will be grown in culture for anticancer evaluation. Research to-date has concentrated mainly on the rapid-growing, relatively abundant cyanophytes found predominantly in terrestrial ecosystems and belonging to the order Nostocales. The proposed research will focus on the slower-growing and rarer blue-green algae, particularly those found in marine environments. Sponges, tunicates, and other marine invertebrates that harbor cyanophytes and prochlorophytes will also be collected for anticancer evaluation. Extracts of the cultured cyanophytes and the marine animals containing algal symbionts will be prepared and tested for cytotoxicity using the KB cell line (a human epidermoid carcinoma of the nasopharynx). The extracts will also be evaluated for tumor-promoting and anti-tumor-promoting activity using the Epstein-Barr virus-induced transformation by 12-0-tetradecanoylphorbol-13-acetate in Raji cells assay. Using these bioassays to monitor fractionation of the active principles in the most promising leads, the cytotoxic, tumor-promoting, and anti-tumor-promoting compounds will be isolated and their molecular structures, including absolute stereochemistries, will be elucidated by a combination of chemical and physical methods. The cytotoxic agents will be evaluated further for selective cytotoxicity in the National Cancer Institute's human cancer cell line panel. For example, the potent cytotoxins in the cultured cyanophytes Scytonema burmanicum (UH isolate D)-4-1) and Plectonema fortii (UH isolate DO-321-2), the algal- containing sponge Sarcotragus sp. for Guam, and that algal-containing didemnid tunicate SG-37 from Guam will be isolated, identified, and evaluated as anticancer agents.

这项研究的主要目标是发现新的天然产物， 蓝绿藻（蓝藻）和具有藻类的海洋动物 可用作治疗癌症或其 预防和/或作为研究化学物质的药理学工具 致癌作用 新分离的蓝绿藻将在 用于抗癌评价的培养物。 迄今为止的研究集中在 主要是在快速生长的，相对丰富的蓝藻发现 主要存在于陆地生态系统中， 念珠藻目 拟议中的研究将集中在生长较慢， 稀有的蓝绿藻，特别是那些在海洋环境中发现的。 海绵类、被囊类和其他海洋无脊椎动物， 蓝藻和原绿藻也将被收集用于抗癌 评价 培养的蓝藻和海洋动物的提取物 将制备含有藻类共生体的混合物并进行细胞毒性测试 使用KB细胞系（人表皮样癌， 鼻咽）。 还将评估提取物的肿瘤促进作用。 和使用EB病毒诱导的抗肿瘤活性 12-0-十四酰基佛波醇-13-乙酸酯转化Raji细胞 比色法 使用这些生物测定来监测活性物质的分馏 原则在最有前途的铅，细胞毒性，肿瘤促进， 和抗肿瘤促进化合物将被分离，并且它们的分子 结构，包括绝对立体化学，将通过以下方式阐明： 化学和物理方法的结合。 细胞毒性剂 将在全国范围内进一步评价选择性细胞毒性。 癌症研究所的人类癌细胞系小组。 比如说 培养的蓝藻缅甸蓝丝藻（Scytonema burmanicum，UH 分离物D）-4-1）和弗氏钝丝藻（UH分离物DO-321-2），藻类- 含有海绵Sarcotragus sp.的关岛， 将从关岛分离，鉴定， 作为抗癌剂进行评价。