ANTICANCER AGENTS FROM BLUE-GREEN ALGAE

蓝绿藻的抗癌剂

• 批准号: 3163668
• 负责人: RICHARD E MOORE
• 金额: $ 15.55万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163668
• 关键词: Cnidaria; Cyanophyta; Ehrlich's tumor; Pacific Islands; antineoplastics; bioassay; cytotoxicity; drug design /synthesis /production; drug metabolism; gel electrophoresis; lymphocytic leukemia; medicinal plants; nuclear magnetic resonance spectroscopy; saltwater environment; thin layer chromatography; toxin

The main goal of this research is to isolate, identify, and evaluate new anticancer compounds from field-collected and cultured blue-green algae (cyanobacteria). Extracts of blue-green algae will be screened for cytotoxicity against human epidermoid carcinoma of the nasopharynx cells (KB) and a mouse fibroblast cell line (NIH3T3) and for antineoplastic activity in vivo against murine P-388 lymphocytic leukemia and murine Lewis lung carcinoma. Using one of more of these bioassays to monitor the fractionation of active extracts, cytotoxic and/or antitumor compounds will be isolated from the algae and their molecular structures, including absolute stereo-chemistries, will be elucidated by a combination of chemical and physical methods. The pure active compounds will be evaluated in other murine tumor systems, viz. B16 melanoma, Ehrlich ascites carcinoma, and Rauscher viral leukemia, for potential use as chemotherapeutic agents in the treatment of human cancer. Mode of action studies will be carried out on the active compounds. Extracts of blue-green algae will also be screened for potential inhibitors of tumor promotion with two bioassays, viz. inhibition of human promyelocytic leukemia (HL-60) cell adhesion by a potent tumor promoter such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibition of specific binding of a potent tumor promoter such as TPA to receptors in a rat embryonic fibroblast cell line (CREF). Several derivatives and analogues of aplysiatoxin, a tumor promoter from the marine blue-green alga Lyngbya majuscula having the same potency as TPA, will be prepared for structure-activity studies and the eventual development of an anti-tumor-promoter (chemopreventitive). Finally antineoplastic agents from certain marine organisms, e.g. palytoxin from the coelenterate Palythoa toxica, will be further evaluated as potential chemotherapeutic drugs.

这项研究的主要目标是分离、识别和评估新的 野外采集和养殖蓝藻中的抗癌化合物 (蓝藻)。蓝藻的提取物将被筛选出 鼻咽细胞对人表皮样癌的细胞毒作用 (KB)和小鼠成纤维细胞系(NIH3T3)并用于抗肿瘤 小鼠P-388淋巴细胞白血病和小鼠Lewis的体内抗肿瘤活性 肺癌。使用一种以上的生物检测方法来监测 活性提取物、细胞毒性和/或抗肿瘤化合物的分级将 从藻类及其分子结构中分离出来，包括 绝对的立体化学，将通过以下组合来阐明 化学和物理方法。将对纯活性化合物进行评估 在其他小鼠肿瘤系统中，即。B16黑色素瘤，艾氏腹水 癌症和Rauscher病毒白血病，可能用作 人类癌症治疗中的化疗药物。行动模式 将对活性化合物进行研究。植物精华 蓝绿藻也将被筛选出潜在的肿瘤抑制物 推广使用两种生物检测方法，即。人早幼粒细胞的抑制作用 白血病(HL-60)细胞与强效促癌剂的黏附 12-O-十四酰佛波醇-13-乙酸酯(TPA)及其特异性抑制作用 大鼠体内TPA等强效促癌物质与受体的结合 胚胎成纤维细胞系(CREF)。几种衍生物和类似物 海洋蓝藻Lyngbya的肿瘤促进剂Aplysiatoxin 与TPA具有相同效力的Majuscula将为 结构-活性研究和AN的最终发展 抗肿瘤促进剂(化学促进剂)。最后是抗肿瘤药物 来自某些海洋生物，例如来自腔肠动物的孢子虫毒素 将进一步评估其为潜在的化疗药物。 毒品。