ANTICANCER AGENTS FROM BLUE-GREEN ALGAE

蓝绿藻的抗癌剂

• 批准号: 3163666
• 负责人: RICHARD E MOORE
• 金额: $ 14.64万
• 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 1989-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163666
• 关键词: Cyanophyta; Ehrlich's tumor; Pacific Islands; 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隔离，识别和评估新的 来自现场收获和培养的蓝绿色藻类的抗癌化合物 （蓝细菌）。 将筛选蓝绿色藻类的提取物 针对鼻咽细胞的人类表皮癌的细胞毒性 （KB）和小鼠成纤维细胞系（NIH3T3）和抗肿瘤 在体内对鼠P-388淋巴细胞性白血病和鼠Lewis的活性 肺癌。 使用此类生物测定中的更多来监视 活性提取物，细胞毒性和/或抗肿瘤化合物的分馏将 从藻类及其分子结构中分离出来，包括 绝对的立体化学化学将通过结合 化学和物理方法。 将评估纯活性化合物 在其他鼠肿瘤系统中，即。 B16黑色素瘤，Ehrlich腹水 癌和Rauscher病毒性白血病潜在用作 化学治疗剂在治疗人类癌症中。 行动方式 研究将在活性化合物上进行。 提取 蓝绿色藻类也将被筛选为潜在的肿瘤抑制剂 促销有两个生物测定，即。抑制人类临时细胞 有效的肿瘤启动子（例如 12-O-四烷酰基-13-乙酸酯（TPA）和抑制特定 有效肿瘤启动子（例如TPA）与大鼠受体的结合 胚胎成纤维细胞系（CREF）。 几个衍生物和类似物 来自海洋蓝绿色藻类lyngbya的肿瘤启动子的Aplysiatoxin Majuscula具有与TPA相同的效力 结构活动研究和最终的发展 抗肿瘤促销（化学预报）。 最后，抗肿瘤剂 来自某些海洋生物，例如腔毒素的腔毒素 Palythoa toxica将进一步评估为潜在的化学治疗性 毒品。