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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李宗徽 | |
dc.contributor.author | Chia-Yu Chen | en |
dc.contributor.author | 陳佳妤 | zh_TW |
dc.date.accessioned | 2021-06-17T03:12:04Z | - |
dc.date.available | 2018-07-19 | |
dc.date.copyright | 2018-07-19 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-16 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69284 | - |
dc.description.abstract | 本研究利用病原菌篩選平臺(Staphylococcus aureus, Escherichia coli, Candida albicans 和 Cryptococcus neoformans)篩選出具有抗菌潛力的海藻源真菌菌株。實驗結果顯示,Acremonium sp. NTU492之粗萃物具有抗Candida albicans 和 Cryptococcus neoformans的效果。因此選擇以頂孢黴菌Acremonium sp. NTU492為目標真菌,以1/2 PDA液態培養與糙米固態培養之後,分離並純化此株真菌的二次代謝物。共計獲得15個化合物,藉由各種光譜資料解析其結構。其中9個為新化合物,分別為acrepeptins A−E(2−6)、acremonisins A−B(12−13)、(4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)、4,4-dihydroxy-6,8-dimethoxy-5-methylisochroman-1-one(15)。另外6個為已知化合物,分別為8-deoxy-trichothecin(1)、cyclo[L-alanyl-L-threonyl-(2S)-2-hydroxy-3-methylbutanoyl-L-isoleucyl-(2S)-2-hydroxy-3-methylbutanoyl](7)、β-alanine, N-[N-[N-[N-[1-(2-hydroxy-4-methyl-1-oxopentyl)-L-prolyl]-L-isoleucyl]-N-methyl-L-valyl]-N-methyl-L-alanyl](8)、guangomides A−B(9−10)和brefeldin A(11)。在抗菌活性上,8-deoxy-trichothecin(1)具有抑制白色念珠菌(C. albicans)、新型隱球菌(C. neoformans)的活性,其最小抑制濃度(MIC)分別為2.0和0.5 μg/mL;brefeldin A(11)具有抑制白色念珠菌的活性,其最小抑制濃度(MIC)為32 μg/mL;(4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)具有抑制新型隱球菌的活性,其最小殺真菌濃度(MFC)為16 μg/mL。在抗癌活性上,8-deoxy-trichothecin(1)對於人類肝癌細胞(hepatocellular carcinoma cells,SK-Hep-1)與人類抗藥性卵巢癌細胞(paclitaxel-resistant ovarian cancer cells,TOV-21G-RT)具有毒殺活性,其半抑制濃度(IC50)分別為2.1與1.8 μM;cyclo[L-alanyl-L-threonyl-(2S)-2-hydroxy-3-methylbutanoyl-L-isoleucyl-(2S)-2-hydroxy-3-methylbutanoyl](7)對於人類肝癌細胞與人類前列腺癌細胞(prostate cancer cells,PC-3)具有毒殺活性,其半抑制濃度(IC50)分別為3.7與6.6 μM;brefeldin A(11)對於人類肝癌細胞與人類前列腺癌細胞(prostate cancer cells,PC-3)具有毒殺活性,其半抑制濃度皆小於1 μΜ;(4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)對於人類肝癌細胞與人類前列腺癌細胞具有毒殺活性,其半抑制濃度分別為1.6與1.7 μM。最後,在抗發炎活性上,acrepeptins A−C(2−4)具有抑制NO產生的活性,於20 μM下抑制NO產生之比例分別為73.3%、58.6%和77.2%。總而言之,本研究共計分離純化15個化合物,並對其結構、化學特性與生物活性進行探究。 | zh_TW |
dc.description.abstract | 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 extracts of liquid (potato dextrose broth) and solid (brown rice) fermented products of Acremonium sp. NTU492, a fungus derived from the red alga Mastophora rosea, were found to exhibit significant growth inhibitory activity against C. albicans and C. neoformans. A series of fractionation and separation was thus undertaken, which has resulted in the isolation and purification of 15 compounds, and their structures were elucidated by spectral analysis. Among these, nine novel compounds included acrepeptins A−E (2−6), acremonisins A−B (12−13), (4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)and 4,4-dihydroxy-6,8-dimethoxy-5-methylisochroman-1-one (15). The other were known compounds, determined to be 8-deoxy-trichothecin (1), cyclo[L-alanyl-L-threonyl-(2S)-2-hydroxy-3-methylbutanoyl-L-isoleucyl-(2S)-2-hydroxy-3-methylbutan -oyl] (7), β-alanine, N-[N-[N-[N-[1-(2-hydroxy-4-methyl-1-oxopentyl)-L-prolyl]-L-isoleucyl]-N-methyl-L-valyl]-N-methyl-L-alanyl] (8), guangomide A (9), guangomide B (10) and brefeldin A (11). In terms of antibacterial activity, 8-deoxy-trichothecin (1) showed activity against Candida albicans and Cryptococcus neoformans with MIC = 2.0 μg/mL and 0.5 μg/mL, respectively; brefeldin A(11)showed activity against Candida albicans with MIC = 32 μg/mL; (4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)showed activity against Cryptococcus neoformans with MFC = 16 μg/mL. In respect of anticancer activity, 8-deoxy-trichothecin (1) showed activity against hepatocellular carcinoma cells (SK-Hep-1) and paclitaxel-resistant ovarian cancer cells (TOV-21G-RT), with IC50 = 2.1 and 1.8 μM, respectively; cyclo[L-alanyl-L-threonyl-(2S)-2-hydroxy-3-methylbutanoyl-L-isoleucyl-(2S)-2-hydroxy-3-methyl butanoyl] (7) showed activity against hepatocellular carcinoma cells and prostate cancer cells (PC-3), with IC50 = 3.7 and 6.6 μM respectively; brefeldin A(11)showed activity against hepatocellular carcinoma cells and prostate cancer cells with both IC50 lower than 1 μΜ; (4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)showed activity against hepatocellular carcinoma cells and prostate cancer cells with IC50 = 1.6 and 1.7 μM respectively. Finally, in regard to anti-inflammatory activity, acrepeptin A−C (2−4) inhibited 73.3, 58.6 and 77.2% of NO production under the concentration of 20 μM. In summary, a total of 15 compounds were isolated, and their structures, chemical properties and biological activities were investigated in this study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T03:12:04Z (GMT). No. of bitstreams: 1 ntu-107-R05b45004-1.pdf: 16323161 bytes, checksum: 4e4659b1c554cd131c5d35af3e4f7479 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 謝辭 ii
中文摘要 iii 英文摘要 v 目錄 viii 表目錄 ix 圖目錄 x 縮寫表 xiii Chapter 1 緒論與研究目的 1 Chapter 2 文獻回顧 5 2.1 菌株分類學和介紹 5 2.2 頂孢黴菌屬真菌成分之文獻回顧 6 Chapter 3 結果與討論 39 3.1 真菌培養醱酵分離流程 39 3.1.1 Acremonium sp.NTU492液態培養分離 39 3.1.2 Acremonium sp.NTU492液態培養分離 41 化合物1−15結構分類 43 3.2 天然物結構解析 46 3.2.1 8-Deoxy-trichothecin(1)之結構解析 46 3.2.2 Acrepeptin A(2)之結構解析 54 3.2.3 Acrepeptin B(3)之結構解析 67 3.2.4 Acrepeptin C(4)之結構解析 78 3.2.5 Acrepeptin D(5)之結構解析 90 3.2.6 Acrepeptin E(6)之結構解析 100 3.2.7 cyclo[L-alanyl-L-threonyl-(2S)-2-hydroxy-3-methylbutanoyl-L-isoleucyl-(2S)-2-hydroxy-3-methylbutanoyl](7)之結構解析 109 3.2.8 β-alanine, N-[N-[N-[N-[1-(2-hydroxy-4-methyl-1-oxopentyl)-L-prolyl]-L-isoleucyl]-N-methyl-L-valyl]-N-methyl-L-alanyl](8)之結構解析 117 3.2.9 Guangomide A(9)之結構解析 126 3.2.10 Guangomide B(10)之結構解析 136 3.2.11 Brefeldin A(11)之結構解析 145 3.2.12 Acremonisin A(12)之結構解析 153 3.2.13 Acremonisin B(13)之結構解析 162 3.2.14 (4R, 7R, 9S, E)-4,7-dihydroxy-9-propyl-2,3,4,7,8,9-hexahydro-2H-oxecin-1-one(14)之結構解析 170 3.2.15 3,3-Dihydroxy-6,8-dimethoxy-5-methylisochroman-1-one(15)之結構解析 179 3.3 化合物活性平臺測試 185 3.3.1 抑菌試驗結果 185 3.3.2 細胞毒性試驗結果 186 3.3.3 一氧化氮抑制與細胞存活率之實驗結果 188 Chapter 4 材料與方法 190 4.1 儀器設備與試劑 190 4.1.1 化合物物理性質測定儀器 190 4.1.2 高效能液相層析系統 190 4.1.3 管柱層析膠體 191 4.1.4 薄層層析 191 4.1.5 試劑耗材與溶劑 191 4.1.6 氨基酸標準品 192 4.2 真菌單離 193 4.2.1 真菌來源 193 4.2.2 真菌培養基 193 4.2.3 藻體衍生真菌的單離 194 4.2.4 菌株培養與萃取 195 4.2.5 粗萃物抗菌活性評估 195 4.3 菌株鑑種 196 4.3.1 菌株親緣關係鑑定 196 4.4 真菌培養 197 4.4.1 液態曝氣培養 197 4.4.2 固態培養基配製 198 4.5 Acremonium sp. NTU492之成分分離與純化 199 4.5.1 液態醱酵萃取物分離流程 199 4.5.2 固態糙米萃取物分離流程 200 4.6 一氧化氮抑制試驗 204 4.6.1 細胞培養 204 4.6.2 Griess reagent assay 204 4.7 抗菌活性試驗 205 4.7.1 細胞培養 206 4.7.2 最小抑制濃度試驗 206 4.8 細胞毒性試驗 206 4.8.1 目的及原理 206 4.8.2 細胞培養 207 4.8.3 Sulforhodamine B(SRB)assay 207 Chapter 5 討論 208 Chapter 6 各成分之物理數據 211 參考文獻 217 | |
dc.language.iso | zh-TW | |
dc.title | 紅藻源真菌株Acremonium sp. NTU492之活性成分研究 | zh_TW |
dc.title | Bioactive constituents from a red alga-derived fungus Acremonium sp. NTU492 | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳日榮,韓玉山,宋秉鈞,蕭哲志 | |
dc.subject.keyword | 天然物,海洋真菌,藻源真菌,NMR,多?類, | zh_TW |
dc.subject.keyword | Natural products,marine fungi,alga-derived fungi,NMR,peptides, | en |
dc.relation.page | 233 | |
dc.identifier.doi | 10.6342/NTU201801553 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-07-16 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 漁業科學研究所 | zh_TW |
顯示於系所單位: | 漁業科學研究所 |
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