(3.238.186.43) 您好!臺灣時間:2021/03/05 22:28
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:郭佳宜
研究生(外文):Kuo, Chia-Yi
論文名稱:台灣產印度塔樹枝葉之天然物研究
論文名稱(外文):Studies on the Natural Products from the Twigs and Leaves of Taiwanese Polyalthia longifolia
指導教授:張誌益林昀生
指導教授(外文):Chang, Chi-ILin, Yun-Sheng
口試委員:徐睿良
口試委員(外文):Hsu, Jue-Liang
口試日期:2017-07-12
學位類別:碩士
校院名稱:國立屏東科技大學
系所名稱:生物科技系所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:106
中文關鍵詞:印度塔樹番荔枝科登革熱人類肝癌細胞株Huh-7NS2B蛋白
外文關鍵詞:Polyalthia longifoliaAnnonaceaedengue feverHuh-7NS2B protein
相關次數:
  • 被引用被引用:0
  • 點閱點閱:48
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
近年來由於全球溫室效應影響,登革熱為目前世界上廣為蔓延之疾病之一,發病率在全球大幅上升,而目前在預防及治療登革熱策略上,極少有疫苗或藥劑,因此開發治療抗登革熱藥物為刻不容緩之事。
印度塔樹 (Polyalthia longifolia) 為番荔枝科 (Annonaceae) 植物,是一種多年生常綠喬木,廣泛分布於熱帶及亞熱帶地區,於傳統上用來治療糖尿病、高血壓、皮膚方面等疾病,並具有抗發炎、抗癌之活性。
過去本植物曾發現內含雙萜類與生物鹼類之化合物,本研究首次發現四個新化合物為雙萜類與生物鹼類化合物相互鏈結之新化合物。目前共鑑定出三個新clerodane 雙萜類與aporphine 生物鹼鏈結化合物,Polyalongirin A-C (1-3) 與一個新clerodane 雙萜類與proaporphine 生物鹼鏈結化合物Polyalongirin D (4)。上述所有化合物皆利用管柱色層分析、高效能液相層析儀與再結晶法等進行分離純化,其結構透過各種物理數據 (紅外線光譜、質譜、紫外線光譜、旋光值),配合核磁共振圖譜,解析其化學結構。再利用X-ray與圓二色光譜確定其絕對立體結構。
在活性試驗中,對登革熱病毒進行初步測試,針對人類肝癌Huh-7
細胞株,以登革熱第二型 (strain 16681) 病毒感染後,分別以Polyalongirin A-C (1-3) 進行登革病毒細胞感染活性試驗,實驗結果發現Polyalongirin B (2) 對NS2B蛋白之表現量具有明顯抑制效果,未來將進一步探討其作用機轉及動物試驗。
In the recent years, due to the greenhouse effect, dengue fever is the most widely spread diseases and its morbidity increased significantly in the world. To date, there are less vaccine or pharmacy to prevent and treat dengue fever, so the development of anti-dengue fever drugs was urgent.
Polyalthia longifolia, belonging to the Annonaceae family, is an everygreen tree that widely distributed in tropical and subtropics region. The species is traditionally used for the treatment of diabetes, hypertension and skin disease and exhibits anti-inflammatory and anticancer activities.
In the past, it had been found diterpenes and alkaloids compounds in this plant. In this study, we found four compounds with diterpene and alkaloid linkage for the first time, containing diterpene and alkaloid compounds linked to each other. Now, we have identified three novel clerdone diterpenes and aporphine alkaloids linked compounds, Polyalongirin A-C (1-3) with a novel clerdone diterpenes and proaporphine alkaloids linked compound, Polyalongirin D (4). Further purification was carried out by column chromatography, high performance liquid chromatograph and recrystallization.
All structures of the compounds were elucidated by NMR spectra and physical data ( IR, mass spectrometry, ultraviolet, optical rotation ). Their absolute structure were determined by X-ray and CD spectrum.
In the activity test, preliminary testing of dengue virus, against the human hepatocyte cell line Huh-7 with dengue fever type 2 (strain 16681) virus infection. Selected compounds were then investigated for their ability to inhibit dengue NS2B protein. Among these compounds, Polyalongirin B (2) exhibited significant inhibitory effects against NS2B protein expression in the infected Huh-7 cells replication. We will further explore the mechanism of action and animal experiments in the future.
摘要....................................................I
Abstract...............................................II
誌謝....................................................Ⅲ
目錄....................................................Ⅳ
圖表目錄.................................................Ⅴ
壹、前言................................................1
一、緒言................................................1
二、植物簡介............................................8
三、研究動機...........................................13
貳、文獻回顧...........................................14
一、番荔枝科暗羅屬.....................................14
二、抗登革熱病毒.......................................30
參、材料與方法.........................................32
一、化合物分離與純化....................................32
(一) 實驗藥品與儀器..................................32
(二) 實驗方法.......................................34
(三) 結構之鑑定.....................................38

二、登革熱病毒之NS2B蛋白表現試驗.........................40
肆、結果 ...........................................41
一、Polyalongirin A (1) 之結構解析......................42
二、Polyalongirin B (2) 之結構解析......................56
三、Polyalongirin C (3) 之結構解析......................69
四、Polyalongirin D (4) 之結構解析......................82
五、Circular Dichroism Spectrum結果....................95
六、登革病毒初步活性試驗結果.............................96
伍、結論................................................97
參考文獻................................................99
作者簡介...............................................106
附錄...................................................107
李惠林、劉棠瑞、黃增泉、小山鐵夫、棣慕華(1979)臺灣植物誌(第一版)。現代關係出版社出版,665頁。

廖日京(1993)台灣木本植物學名目錄。台灣大學森林學系出版,212頁。

胡小婷(2005)登革病毒非結構性蛋白之昆蟲細胞大量表現系統。行政
院衛生署九十四年度委託研究計畫。計畫編號: DOH94 - DC –1012。

章錦瑜編著,「景觀植物」,第一卷,淑馨出版社出版,p.177,1987。

中國科學院昆明植物研究所編著(1991)雲南植物誌(第五卷)。中國科
學出版社出,809頁。

施純明、陳蕙如、李曉輝、李淑芬、王嘉媜(1999)登革熱病毒快速診
斷定型方法之發展與建立。行政院衛生署八十八年度科技研究發展
計畫結果報告。計畫編號: DOH88 - TD - 1002。

Anil, P. Phadnis, Sarita A.(1988)Patwardhan,Clerodane Diterpenoids from Polyalthia longifolia. Phytochemistry. 27(9):2899-2901.

Chee, C. F., Zain, S. M., Rahman, N. A.(2011) Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors -A Computational Approach. International Journal of Molecular Sciences. 12:1089- 1100.

Chen, C.Y., Chang, F.R., Shih,Y.C.(2000)Cytotoxic Constituents of Polyalthia longifolia var. pendula. J. Nat. Prod. 63:1475-1478.

Flamand, M., Megret, F., Mathieu, M., Lepault, J., Rey, F. A., Deubel, V. (1999)Dengue virus type 1 nonstructural glycoprotein NS1 is secreted from mammalian cells as a soluble hexamer in a glycosylation- dependent fashion. J Virol. 73:6104-10.

Francisco Javier Diaz C.(2007)Microbiología de las infecciones humanas. Fundamentos Básicos de Medicina, Spain.

Frimayanti, N., Chee, C. F., Zain, S. M., Rahman, N. A.(2011) Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors -A Computational Approach. International Journal of Molecular Sciences.12:1089- 1100.

Ghani, N.A. Ahmat, N. Ismail, N.H.(2012)Chemical Constituents and Cytotoxic Activity of Polyalthia cauliflora var. cauliflora. Science Alert. 6:74-82.

Gibbons, RV, Vaughn, DW(2002)Dengue: an escalating problem. BMJ. 324:15636.

Goyal, M. M. Gupta Achla.(1987)Antibacterial activity of some active principles of Polyathia longifolia leaves. Indian J. Pharmac.19:216-220.

Guzman, M.G., Halstead, S.B., Artsob, H., Buchy, P., Farrar, J., Gubler, D.J(2010)Dengue, a continuing global threat. The Journal of Nature Reviews Microbiology.8:s7-16.

Hui-Yingli , Nan-Jun Sun, Yoshikkia Shiwadlai. (1993) Anti-AIDS Agents 9.' Suberosol, A New C31 Lanostane-Type Triterpene and Anti-HIV Principle From Polyalthia Suberosa. J. Nat. Prod. 56(7):1130-1133

Hussin A. Rothan Hirbod Bahrani, Noorsaadah Abd Rahman, Rohana Yusof.(2014) Identification of natural antimicrobial agents to treat dengue infection: In vitro analysis of latarcin peptide activity against dengue virus. BMC Microbiology. 14:140.

Jolad, S. D., Hoffmann, J. J., Schram, K. H., Cole, J. R., Tempesta, M. S., Kriek, G. R., Bates, R. B.(1982)Uvaricin, a new antitumor agent from Uvaria accuminata (annonaceae). Journal of Organic Chemistry. 47(16):3151-3153.

Joseph, D. Connonlly, MD. Enamul Haque, A. (1996) Two 7,7'-Bisdehydro Aporphine Alkaloids from Polyalthia Bullata. Phytochemistry. 43(1):295-297.

Jossang, A. Leboeuf, M. Cave, A.(1984)Alcaloides Annoacees, L’: Alcaloides De Polyalthia Cauliflora. J. Nat. Prod. 47(3):504-513.

Kanokmedhakul,S., Kanokmedhakul,K,. Ohtani, Ikuko I.(1998)A diynoic acid from Polyalthia evecta. Phytochemistry. 47:131-133.

Kinoshita, H., Mathenge, E. G. M., Hung, N. T., Huong,V. T. Q., Kumatori,A., Yu,F.(2009)Isolation and Characterization of Two Phenotypically Distinct Dengue Type-2 Virus Isolates from the Same Dengue Hemorrhagic Fever Patient. Japanese Journal of Infectious Diseases. 62:343-350.

Kofi Annan, Edmund Ekuadzi, Cindy Asare.(2015)Antiplasmodial constituents from the stem bark of Polyalthia longifolia var pendula. Phytochemistry Letters. 11:28–31.

Koneni V. Sashidhara, Suriya P. Singh, Ruchir Kant.(2010)Cytotoxic cycloartane triterpene and rare isomeric bisclerodane diterpenes from the leaves of Polyalthia longifolia var. pendula. Bioorganic & Medicinal Chemistry Letters. 20:5767–5771.

Koneni V. Sashidharaa, Suriya P. Singha, Anuj Srivastavab, Anju Purib.(2011)
Identification of the Antioxidant Principles of Polyalthia Longifolia Var. Pendula Using TEAC Assay. Nat Prod Res.25(9):918-926

Kuo, R. Y. Cheng, F. R. Wu, Y. C.(2002)Chemical constituents and their pharma

Kummerer, B.M., Rice, C.M.(2002)Mutations in the Yellow Fever Virus Nonstructural Protein NS2A Selectively Block Production of Infectious Particles. J Virol. 76:4773-4784.

Leboeuf, M., Cavé, A., Bhaumika, P.K., Mukherjeea, B., Mukherjeeb, R. (1982)The phytochemistry of the Annonaceae. Phytochemistry. 21: 2783-2813.

Lindenbach, B.D., Rice, C.M.(1999)Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function. J Virol. 73:4611-21.

Li, H., Clum, S., You, S., Ebner, K. E., Padmanabhan, R.(1999)The serine protease and RNA-stimulated nucleoside triphosphatase and RNA helicase functional domains of dengue virus type 2 NS3 converge within a region of 20 amino acids. J Virol. 73:3108-16

Lue, Q. Mu, H. L. Zheng, C. M. (2015)24-Methylene Tetracyclic Triterpenes from Polyalthia Lancilimba. Phytochemistry.49(7):2053-2056.
.
Manasa, M. Vivek, M.N.(1987) Antibacterial activity of some active principles of Polyathia longifolia leaves. Indian J. Pharmac. 19:216-220.

M.Carmen González, Miguel AngelSentandreu.(1996)Prenylated benzopyran derivatives from two Polyalthia species. Phytochemistry.43(6)1361-1364

Miller, S., Kastner, S., Krijnse-Locker, J., Buhler, S., Bartenschlager, R.(2007)The non-structural protein 4A of dengue virus is an integral membrane protein inducing membrane alterations in a 2K-regulated manner. J Biol Chem. 282:8873-82.

Munoz-Jordan, J. L., Laurent-Rolle, M., Ashour, J., Martinez-Sobrido, L., Ashok, M., Lipkin, W. I., Garcia-Sastre, A.(2005)Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 79:8004-13.

Neni Frimayanti, Chin Fei Chee,(2011) Design of New Competitive Dengue
Ns2b/Ns3 Protease Inhibitors—A Computational Approach. Int. J. Mol. Sci. 12:1089-1100.

Noisakran, S.&Perng,G. C.(2007) Alternate Hypothesis on the Pathogenesis of Dengue Hemorrhagic Fever (DHF)/Dengue Shock Syndrome (DSS) in Dengue Virus Infection. The Journal of Experimental Biology and Medicine. 233(4):401- 408.

Nomaguchi, M., Ackermann, M., Yon, C., You, S., Padmanbhan, R.(2003) De Novo Synthesis of Negative-Strand RNA by Dengue Virus RNA-Dependent RNA Polymerase In Vitro: Nucleotide, Primer, and Template Parameters. J Virol. 77:8831-8842.

Noriyukihara, Hitomi Asaki, Yoshin Orifujimoto.(1995)Clerodane and Ent-Halimane Diterpenes from Polyalthia longifolia. Phytochemistry. 38(1):189-194.

Nozoe, T.(1934)Alkaloids the Annonaceae, annomontine and methoxy annomontine, two new pyrimidine-β-carboline type. J. Chem. Soc. Japan 55:224-227

Padmaa, M. Paarakh1, R. L. Khosa.(2009)Phytoconstituents from the genus Polyalthia – a review. Journal of Pharmacy Research. 2(4):594-605.

Rothan, H.A., Zulqarnain, M., Ammar, Y.A., Tan, E.C., Rahman, N.A. Yusof, R.(2014)Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay. Tropical Biomedicine. 31(2): 286–296

Róbson Ricardo Teixeira, Wagner Luiz Pereira, Ana Flávia Costa da Silveira Oliveira, Adalberto Manoelda Silva, André Silva de Oliveira, Milene Lopes da Silva.(2014)Natural Products as Source of Potential Dengue Antiviral Molecules. 19:8151-8176

Sashidhara, K.V.(2011)Identification of the Antioxidant Principles of Polyalthia Longifolia Var. Pendula Using TEAC Assay. Nat Prod Res. 25 (9): 918-926.

Seikuo Nakamura, Souichi Nakashima(2013)Alkaloid constituents from flower buds and leaves of sacred lotus with melanogenesis inhibitory activity in B16 melanoma cells. Biorganic&Medicinal Chemistry. 21:779-787.

Shunichi Manabe, Crikao Nishino.(1986)Stereochemistry of cis-clerodane diterpene, Tetrahedron. 42(13):3461- 3470

Sirinapa Nantapap, Kallaya Sangrueng.(2015)Chemical Constituents from Aerial Parts of Polyalthia Evecta Finet&Gagnep. Var. Attopeuensis. Int. J. Chem.13(4):1705-1712.

Tung-Ho Wu, Yung-Yi Cheng, Chao-Jung Chen.(2014)Three New Clerodane
Diterpenes from Polyalthia longifolia var. pendula. Molecules. 19:2049-2060.

Vı´ctor Fajardo, Marisel Araya, Pedro Cuadra.(2009) Pronuciferine N-Oxide, a Proaporphine N-Oxide Alkaloid from Berberis coletioides. J. Nat. Prod. 72:1355–1356.

Yang C. C., Hsieh Y. C., Lee S. J.(2011) Novel Dengue Virus-Specific NS2B/NS3 Protease Inhibitor, BP2109, Discovered by a High-Throughput Screening Assay. Antimicrobial agents and chemotherapy. 55(1): 229–238.

Yangchang Wu, Chang-Yih Duh(1990)Two New Natural Azafluorene Alkaloids and A Cytotoxic Aporphine Alkaloid from Polyalthia Longifolia. J. Nat. Prod. 53(5):1327-1331.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
無相關點閱論文
 
系統版面圖檔 系統版面圖檔