深海来源的微生物抗肿瘤活性筛选及次级代谢产物的初步研究.doc

深海来源的微生物抗肿瘤活性筛选及次级代谢产物的初步研究赵博宇，朱天骄，顾谦群*， （教育部海洋药物重点实验室，中国海洋大学医药学院，青岛，266003)摘要：目的 对来自深海的海水、海泥样品进行了微生物分离并通过抗肿瘤活性筛选获得活性菌株，并研究活性菌株的次级代谢产物。方法 从样品中选择性分离得到真菌，采用对分离得到真菌的发酵产物进行抗肿瘤活性筛选；采用分离手段对菌株发酵产物进行了活性追踪分离，通过理化性质及波谱学手段进行化学结构鉴定结果 从深海来源的中共分离获得29株真菌，其中7株具有细胞毒活性；从活性菌株的发酵产物中分离得到个单体化合物（1-），其化学结构分别鉴定为Desoxybrevianamide E (1)，8, 9-dehydro-12, 13-dehydro-Desoxybrevianamide E (2), 8, 9-dehydro-12- hydroxyl-Desoxybrevianamide E (3), 8, 9-dehydro-12- methoxyl-Desoxybrevianamide E (4), Desoxybrevianamide E (5), 5-methoxysterigmatocystin (6), 5, 4’-demethoxylsterigmatocystin (7), 5, 4’-demethoxyl-sterigmatocystin A (8), 4’-methoxylsterigmatocystin (9), averufin (10), 其中化合物1-4、7-9为新化合物。 关键词：深海来源真菌；次级代谢产物；抗肿瘤活性 Antitumor screening of deep ocean water and sediment derived fungi and primary investigation of their secondary metabolites CAI Sheng-xin, ZHAO Bo-yu, ZHU Tian-jiao, GU Qian-qun * (Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China) ABSTRACT: OBJECTIVE The cytotoxic microbial strains isolated from the deep ocean water and sediments were screened, and the secondary metabolites of active fungus 6a were investigated. METHODS Active microbial strains were screened using chronic medulla leucocythemia (K562) cell line. Bioactive fractions were obtained from the crude extract of 6a through a bioassay-guided fractionation and the chemical constituents of the fractions were investigated and purified by the combined use of column chromatography with silica gel and Sephadex LH-20, the preparative HPLC. Their structures were established by spectroscopic methods. RESULTS AND CONCLUSION Twenty nine strains of fungi were isolated. Among them, seven strains showed cytotoxic activities. Ten compounds (1-10) were isolated from the active strain 6a and identified as 8, 9-dehydro-Desoxybrevianamide E (1)，8, 9-dehydro-12, 13-dehydro-Desoxybrevianamide E (2), 8, 9-dehydro-12- hydroxyl-Desoxybrevianamide E (