两株海洋微生物抗肿瘤次级代谢产物的阳研究-海洋科学专业毕业论文.docx

浙江大学硕士学位论文 浙江大学硕士学位论文 摘要 摘要 本论文对源自浙江省洞头县海洋沉积物的38株海洋真菌发酵物进行了抗肿 瘤活性筛选，选择其中2株具有显著抗肿瘤活性的菌株(Penicillium sp．DT-F27 和Penicillium sp．DT-F29)，分别采用摇床培养和静置培养(PDB培养基)发酵， 从发酵液的乙酸乙酯提取物中分离鉴定了26个化合物，并对得到的化合物进行 了初步的抗肿瘤活性分析。 采用硅胶柱色谱、反相高效液相制备色谱以及重结晶等方法分离纯化，应用 波谱技术解析化合物结构。从Penicillium sp．DT-F29静置培养的PDB发酵液中分 离鉴定了10个化合物，包括4个新化合物7。7-dimethoxybrefeldin C(2)， 6a-hydroxybrefeldin C(3)，4-epi-1 5-epi—brefeldin A(4)，4-epi-8a-hydroxy- 15一epi．brefeldin C(5)和6个已知化合物，其中brefeldin A(6)(IC500．2 grnol／L) 和7-epi-brefeldin A(7)(IC50 5．2 lamol／L)具有显著抑制肿瘤细胞H1975生物活 性。从Penicillium sp．DT-F27摇床培养的PDB发酵液中分离鉴定了16个化合物， 包括14个肽类化合物、1个甾醇和1个萘满酮类化合物(trans．(3RS,4RS)． 3,4一dihydro-3，4，8-trihydroxynaphthalen一1(2／-／)一one)，其中麦角甾醇(11)和 3-0．methylvifidicatin(13)有一定的抗肿瘤活性，浓度为1 Irtmol／L时，对PC3细 胞的抑制率分别为45．6％和34．8％。 关键词： 青霉菌，次级代谢产物，抗肿瘤 Ⅱ 万方数据 浙江大学硕士学位论文 浙江大学硕士学位论文 Abstract Abstract Two microoganisms were selected(Penicillium sp．DT-F27 and Penicillium sp． DT-F29)from 38 sediment-derived fungi from Dongtou，Zhejiang by screening antitumor activity．The fungi were cultured in PDB medium with shaking or stationary condition．26 compounds were identified from ethyl acetate extract of the broth and were subjected to a preliminary evaluation of antitumor activity． Compounds were purified through silica gel，reversed phase preparative HPLC and recrystallization etc．The structures were determined by extensive spectroscopic methods．1 0 compounds were separated from static fermentation broth of Penicillium sp．DT-F29，including 4 new compounds 7，7-dimethoxybrefeldin C(2)， 6a—hydroxybrefeldin C(3)，4-epi一1 5一epi-brefeldin A(4)，4-epi一83一hydroxy- 15一epi-brefeldin C(5)and 6 known compounds，in which brefeldin A(6)(ICso0．2 “rnol／L)and 7-epi-brefeldin A(7)(IC50 5．2 rtmol／L)showed significant anti·tumor bioactivity against H 1 975 cell line．1 6 compounds were identified from the broth of Penicillium sp．DT-F27 cultured in shaker,in