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三株深海真菌次级代谢产物及其生物活性研究; Secondary Metabolites from Three Deep-Sea-Drived Fungi Strains and Their Biological Activities
Thesis Advisor章卫民
Degree Discipline生物工程
Keyword深海真菌 次生代谢产物 生物活性
Abstract海洋占地球表面的70%,拥有丰富的微生物资源。海洋特殊的环境,像低温、无光照、高压等,使得海洋微生物产生了独特的代谢机制,进而使得海洋微生物产生有别于陆地的结构特异、生物活性独特的次级代谢产物。在过去几十年里,从海洋微生物中发现了很多具有药物活性的化合物,目前已经有一些来源于海洋微生物的活性分子被用来治疗疾病,海洋微生物已经成为天然产物研究的重要资源。海洋真菌作为海洋微生物中的重要成员,也是新的活性先导化合物的重要来源。为了寻找具有生物活性的先导化合物,本论文对分离自南海深海沉积物的真菌Dichotomomyces cejpii FS110和Cladosporium perangustum FS62与分离自印度洋深海沉积物的真菌Penicillium purpurogenum FS533的次级代谢产物进行了系统研究,并对分离到的部分单体化合物进行了细胞毒、抗菌以及酶抑制活性研究。 本实验采用正相与反相C18硅胶柱色谱、Sephadex LH-20凝胶柱色谱、HPLC等各种色谱学等方法,从这三株海洋真菌的发酵提取物中共得到32个化合物,采用各种现代波谱技术(ESI-MS、HRESIMS、1D NMR、2D NMR、CD和单晶衍射等)结合理化性质,阐明了这32个化合物的结构(图1、图2和图3),其中11个化合物为新化合物,2个化合物为新天然产物。对分离到的部分单体化合物进行了细胞毒、抗菌和酶抑制活性评价。结果表明,化合物9、18、20、21对肿瘤细胞株SF-268、MCF-7、NCI-H460、HepG-2具有较好的抑制活性,化合物9对以上4种肿瘤细胞株的IC50值分别为35.42、30.00、>100、37.30 μM,化合物18对以上4种肿瘤细胞株的IC50值分别为3.56、4.49、12.28、3.02 μM,化合物20对以上4种肿瘤细胞株的IC50值分别为54.38、48.47、>100、30.47 μM,化合物21对以上4种肿瘤细胞株的IC50值分别为33.58、37.50、63.28、34.78 μM。化合物18对Candida albicans、Trichoderma viride、Aspergillus niger和Aspergillus flavus植物病原真菌,以及病原真菌新月弯孢霉 、胶孢炭疽菌、链格孢和柱枝双胞霉具有较好的抑制活性,MIC值分别为80、80、60和60,以及101.8、95.3、96.1和86.5 μg/mL。化合物9具有显著的α-葡萄糖苷酶抑制活性,IC50值为137.98 μM。 综上所述,本研究从海洋真菌FS110、FS62和FS533中共分离并鉴定了32个化合物,其中11个为新化合物,2个为新天然产物,具有细胞毒活性的化合物4个,具有抗菌活性的化合物1个,α-葡萄糖苷酶抑制活性的化合物1个,为海洋真菌资源的开发利用提供了科学依据。
Other AbstractOceans, which cover more than 70% of the earth’s surface, are rich in microorganism resources. Some of these marine species survive in a stressful habitat, under cold, lightless and high-pressure conditions. These factors have resulted in the development of unique metabolisms, which result in the production of novel metabolites that differ from terrestrial organisms. Over the last several decades, numerous compounds have been found in marine organisms with interesting pharmaceutical activities. Marine organisms are important sources of bioactive molecules that have been used to treat various diseases. As an important member of marine microorganism, marine fungi have been considered an important source of bioactive leading compounds. In order to looking for new bioactive leading compounds from marine fungi, a study on three marine fungi strains (Dichotomomyces cejpii FS110, Cladosporium perangustum FS62 and Penicillium purpurogenum FS533) were carried out. Most of the isolated compounds were screened on their cytotoxic, anti-fungi and enzyme inhibition activities. 32 compounds were isolated from the fermentation extracts of the three marine fungi strains by repeated column chromatography (CC) on silica gel, RP-18, and Sephadex LH-20, HPLC, as well as by preparative thin layer chromatography, recrystallization and so on. The structures of these compounds were elucidated by means of spectroscopic techniques, including ESI-MS, HRESIMS, 1D-NMR (1H-NMR, 13 C-NMR and DEPT) and 2D-NMR (1H?1H COSY, HSQC, HMBC and NOESY) as well as chemical method. Totally, 32 compounds were structurally elucidated (see Fig.1, Fig.2 and Fig.3), with 11 new compounds and 2 new natural products. Most of these compounds were evaluated for their cytotoxic, anti-fungi and anti-α-glucosidase and anti-phenylalaninase activities. The results indicated that compound 9 showed mediate cytotoxicity against SF-268, MCF-7, NCI-H460 and HepG-2 cell lines with IC50 values of 35.42、30.00、>100 and 37.30 μM respectively. Compound 18 exhibited strong cytotoxicity against the above tumor cell lines with IC50 values of 3.56、4.49、12.28 and 3.02 μM respectively. Compound 20 displayed mediate cytotoxicity against the four tumor cell lines with IC50 values of 54.38、48.47、>100 and 30.47 μM respectively. Compound 21 showed cytotoxicity against these tumor cell lines with IC50 values of 33.58、37.50、63.28 and 34.78 μM respectively. Compound 18 showed anti-fungi activities against plant pathogenic fungi Candida albicans, Trichoderma viride, Aspergillus niger and Aspergillus flavus, with MIC values of 80, 80, 60 and 60 μg/mL, respectively, and against human pathogenic fungi Curvularia lunata, Colletotrichum gloeosporioides, Alternaria alternata and cylindrocladium, with MIC values of 101.8, 95.3, 96.1 and 86.5 μg/mL, respectively. Compound 9 showed significant α-glucosidase inhibitory activity, with IC50 value of 137.98 μM. Summarily, 32 compounds were isolated and identified from strains Cladosporium perangustum FS62, Dichotomomyces cejpii FS110 and Penicillium purpurogenum FS533, with 11 new compounds, 2 new natural products, 4 compounds possessing cytotoxic activities, 1 compound possessing anti-fungal activities and 1 compound possessing siginificant anti-α-glucosidase activity. This study provided a scientific basis for utilizing marine fungi efficiently.
Document Type学位论文
Recommended Citation
GB/T 7714
范震. 三株深海真菌次级代谢产物及其生物活性研究, Secondary Metabolites from Three Deep-Sea-Drived Fungi Strains and Their Biological Activities[D],2016.
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