ANTICANCER AGENTS FROM BLUE-GREEN ALGAE

蓝绿藻的抗癌剂

• 批准号: 3163667
• 负责人: RICHARD E MOORE
• 金额: $ 15.65万
• 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/3163667
• 关键词: 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.

本研究的主要目的是分离、鉴定和评价新的 从野外采集和培养的蓝绿藻中提取的抗癌化合物 （蓝细菌）。 蓝绿藻的提取物将被筛选， 对人鼻咽上皮样癌细胞的细胞毒作用 (KB)和小鼠成纤维细胞系（NIH 3 T3）， 对鼠P-388淋巴细胞白血病和鼠刘易斯的体内活性 肺癌 使用这些生物测定中的一种或多种来监测 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 绝对立体化学，将通过以下的组合来阐明： 化学和物理方法。 将评价纯活性化合物 在其它鼠肿瘤系统中，即B16黑色素瘤、埃利希腹水 癌和Rauscher病毒性白血病，用于潜在地用作 在治疗人类癌症中的化学治疗剂。 作用模式 将对活性化合物进行研究。 提取物 蓝绿藻也将被筛选出潜在的肿瘤抑制剂 用两种生物测定促进，即抑制人早幼粒细胞 白血病（HL-60）细胞粘附的有效肿瘤促进剂，如 12-O-十四酰基佛波醇-13-乙酸酯（TPA）和特异性抑制 大鼠中有效肿瘤促进剂如TPA与受体的结合 胚胎成纤维细胞系（CREF）。 几种衍生物和类似物 海洋蓝绿鞘丝藻中的一种肿瘤促进因子- 具有与TPA相同效力的majuscula，将制备用于 结构活性研究和最终开发的一个 抗肿瘤促进剂（化学预防）。 最后，代理商 来自某些海洋生物的，例如来自腔肠动物的海葵毒素 Palythoa toxica将作为潜在的化疗药物进行进一步评估 毒品