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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳世雄(Shih-Hsiung Wu) | |
| dc.contributor.author | Tzu-Jie Huang | en |
| dc.contributor.author | 黃子傑 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:47:30Z | - |
| dc.date.available | 2021-08-09 | |
| dc.date.copyright | 2018-08-09 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-03 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79143 | - |
| dc.description.abstract | 自從抗生素被應用在臨床治療後，過度使用抗生素也衍生出越來越多的抗藥性菌株。在流行病學上，雖然抗藥性真菌並非相當的盛行，但超過半數的抗真菌用藥已經被證實無法有效的抑制病原真菌，因此發展新的抗生素對抗耐藥性真菌是一個刻不容緩的議題。天然物因具備高度的結構多樣性，故一直以來都被視為重要的新藥來源。在本研究中，利用白色念珠菌 (Candida albicans ) 以及隱球菌 (Cryptococcus neoformans) 作為活性的篩選平台，從海洋源真菌Trichoderma brevicompactum NTU439 當中，分離純化出具有活性且未被發表的化合物，做為新的抗真菌藥物使用。在這次的實驗當中分離出9個化合物，並利用光譜學的方法鑑定出其化學結構，其中化合物 1 (trichobrevidin A)、2 (trichobrevidin B) 和8 (alamethicin F50/J) 為新化合物。在活性方面，化合物3 以及 5-9 都具有抑制病原真菌的能力; 除此之外，化合物 2 則具有抗肝細胞癌的活性。 | zh_TW |
| dc.description.abstract | Ever since the introduction of antibiotics into clinical practice, the overuse of antibiotics has led to the alarming emergence of drug resistance throughout many infectious microorganisms. Though the occurance of antifungal resistance is less frequent than antibacterial resistance, more than half of antifungal agents fail to efficiently inhibit clinical fungal infections. Therefore, there is an urgent need for new antifungal agents to overcome drug resistance in fungi. Natural products with diverse set of structures have been recognized as a reservoir for new therapeutic entities for given bioactivities. In our study, we utilized fungal pathogens Candida albicans and Cryptococcus neoformans as a selection platform for bioassay-guided screening in order to isolate bioactive and hitherto unreported compounds from marine-derived Trichoderma brevicompactum NTU439. Nine compounds were obtained and identified by spectroscopic analysis, which revealed three new compounds 1 (trichobrevidin A), 2 (trichobrevidin B) and 8 (alamethicin F50/J). Compounds 3 and 5-9 showed biological activities against pathogenic fungi. In addition, compound 2 showed anti-hepatocellular carcinoma activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:47:30Z (GMT). No. of bitstreams: 1 ntu-107-R05b46017-1.pdf: 20107398 bytes, checksum: 461d8fc3fa59db5360ac391701994195 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員會審定書 ii
誌謝 iii 摘要 iv ABSTRACT v TABLE OF CONTENTS vi LIST OF FIGURES ix LIST OF TABLES xiv LIST OF ABBREVIATIONS xvi 1. INTRODUCTION 1 1.1 Antifungal Resistance Is a Global Challenge 1 1.2 Natural Products Play a Vital Role in Drug Discovery 3 1.3 Objective 4 2. LITERATURE REVIEW 5 3. MATERIALS AND METHODS 40 3.1 Fungal Sources 40 3.2 Fermentation 40 3.2.1 Liquid Fermentation 40 3.2.2 Solid Fermentation 40 3.3 Extraction 41 3.3.1 Extraction of Liquid Fermentation 41 3.3.2 Extraction of Solid Fermentation 41 3.4 Chromatography 41 3.4.1 Column Chromatography 41 3.4.2 Thin Layer Chromatography 42 3.5 Spectroscopic Tool 42 3.5.1 Nuclear Magnetic Resonance 42 3.5.2 Mass Spectrometry 43 3.5.3 Fourier Transform Infrared Spectroscopy 43 3.5.4 Optical Rotation 43 3.6 In Vitro Bioactivity Test 44 3.6.1 Disk Diffusion Assays 44 3.6.2 Minimum Inhibitory Concentrations 44 3.6.3 Sulforhodamine B Assays 45 4. RESULTS 46 4.1 Optimal Fermentation Condition for Trichoderma brevicompactum 46 4.2 Flow Chart for Separation Process of Trichoderma brevicompactum 48 4.2.1 Flow Chart of Compound Purification from T. brevicompactum by Liquid Fermentation 48 4.2.2 Flow Chart of Compound Purification from T. brevicompactum by Solid Fermentation 49 4.3 Structure Elucidation of Compound 1 50 4.4 Structure Elucidation of Compound 2 58 4.5 Structure Elucidation of Compound 3 65 4.6 Structure Elucidation of Compound 4 73 4.7 Structure Elucidation of Compound 5 92 4.8 Structure Elucidation of Compound 6 97 4.9 Structure Elucidation of Compound 7 101 4.10 Structure Elucidation of Compound 8 105 4.11 Structure Elucidation of Compound 9 111 4.12 Antimicrobial Activities of Compounds 1-9 115 4.13 Cytotoxicity Activities of Compounds 1-2 116 5. DISCUSSION 117 5.1 Review of Trichodermin 117 5.2 Review of Alamethicin 118 5.3 Biosynthetic Pathway of Compounds 1 and 3 119 5.4 Biosynthesis of Compounds 4-9 120 6. REFERENCES 122 7. APPENDIX 137 | |
| dc.language.iso | en | |
| dc.subject | 二次代謝物 | zh_TW |
| dc.subject | 海洋源真菌Trichoderma brevicompactum | zh_TW |
| dc.subject | 抗真菌藥物 | zh_TW |
| dc.subject | 抗藥性 | zh_TW |
| dc.subject | 天然物 | zh_TW |
| dc.subject | marine-derived Trichoderma brevicompactum | en |
| dc.subject | secondary metabolites | en |
| dc.subject | natural products | en |
| dc.subject | drug resistance | en |
| dc.subject | antifungal agents | en |
| dc.title | 海洋源真菌Trichoderma brevicompactum NTU439之二次代謝產物之生物活性及化學結構分析 | zh_TW |
| dc.title | Biological Activities and Chemical Structures of Secondary Metabolites Isolated from Marine-Derived Fungus Trichoderma brevicompactum NTU439 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 梁博煌(Po-Huang Liang),林曉青(Hsiao-Ching Lin),李宗徽(Tzong-Huei Lee) | |
| dc.subject.keyword | 海洋源真菌Trichoderma brevicompactum,抗真菌藥物,抗藥性,天然物,二次代謝物, | zh_TW |
| dc.subject.keyword | marine-derived Trichoderma brevicompactum,antifungal agents,drug resistance,natural products,secondary metabolites, | en |
| dc.relation.page | 143 | |
| dc.identifier.doi | 10.6342/NTU201802406 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-03 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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