- 學位論文
石蓴衍生真菌株Aspergillus terreus NTU243之成分研究
Chemical Constituents from a Fungal Strain Aspergillus terreus NTU243 Derived from Ulva lactuca
摘要
本研究利用病原菌篩選平台 (Escherichia coli, Staphylococcus aureus, Cryptococcus neoformans和Candida albicans) 來篩選具有抗菌潛力的海藻源真菌株。實驗結果顯示，由石蓴 (Ulva lactuca) 單離出之衍生真菌株Aspergillus terreus NTU243之粗萃物具有抗S. aureus和C. albicans的效果，後續選擇土麴黴A. terreus NTU243進行天然物研究，以液態和糙米固態培養之後，分離並純化此株真菌的次級代謝物。共計獲得16個化合物，藉由各種光譜資料解析其結構。其中4個為新化合物，分別為aspulvinones S - V (10 - 13)，另外12個為已知化合物，分別為butyrolactone I (1)、terretonin D (2)、lovastatin acid (3)、monacolin K methyl ester (4)、(+)-terretonin (5)、(+)-terretonin-A (6)、butyrolactone V (7)、butyrolactone IV (8)、butyrolactone II (9)、aspulvinone G (14)、(+)-terrein (15) 和4,4'-dihydroxybiphenyl (16)。所有純物質在各種活性平台的評估上，得知化合物1、13和15具有抑制小鼠神經膠細胞BV-2產生一氧化氮的效果，於10 µM下抑制NO產生的比例分別為34.5%、45.0%和49.2%；所有化合物對人類急性骨髓性白血病單核球細胞THP-1皆不具顯著的細胞毒性；化合物12和13可以抑制MMP-9蛋白的表現與活性，於10 µM下抑制基質金屬蛋白酶MMP-9產生的比例分別為56.0%和67.8%。
並列摘要
Marine fungi have been regarded as an under-explored source of structurally interesting and bioactive natural products with the potential to provide attractive lead compounds for drug discovery. In this study, a number of alga-derived fungal strains were isolated from marine algae collected from northeastern coast of Taiwan. In the preliminary antimicrobial screening against bacteria and fungi, including Escherichia coli, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans, the ethyl acetate extract of solid (brown rice) fermented products of Aspergillus terreus NTU243, a fungus derived from a marine green alga Ulva lactuca, was found to exhibit significant antimicrobial activities against S. aureus and C. albicans. Therefore, bioassay-guided separations of the active principle from liquid and solid fermented products of Aspergillus terreus NTU243 was undertaken, which has resulted in the isolation and purification of 16 compounds. Their structures were elucidated by spectroscopic analysis to be four new aspulvinones S - V (10 - 13) as well as butyrolactone I (1), terretonin D (2), lovastatin acid (3), monacolin K methyl ester (4), (+)-terretonin (5), (+)-terretonin-A (6), butyrolactone V (7), butyrolactone IV (8), butyrolactone II (9), aspulvinone G (14), (+)-terrein (15), and 4,4'-dihydroxybiphenyl (16). All the isolates were assessed for anti-inflammatory activity by measuring the amount of NO production in LPS-induced BV-2 cells, and compounds 1, 13, 15 inhibited 34.5, 45.0 and 49.2%, respectively, of NO production under the concentration of 10 µM. All the compounds showed no cytotoxicity toward human monocytic cell THP-1 derived from an acute monocytic leukemia, and compounds 12 and 13 inhibited 56.0 and 67.8 % of MMP-9 production in THP-1 cells under the concentration of 10 µM, respectively.