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研究生:陳怡曉
研究生(外文):I-Hsiao Chen
論文名稱:假衛矛屬植物化學成分及其細胞毒殺之研究
論文名稱(外文):Chemical Constituents and Cytotoxicity of Microtropis Species
指導教授:吳永昌
指導教授(外文):Yang-Chang Wu
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:天然藥物研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:401
中文關鍵詞:衛矛科福建賽衛矛日本賽衛矛三萜HDAC
外文關鍵詞:CelastraceaeMicrotropis fokienensisMicrotropis japonicatriterpenesHDAC
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本研究進行台灣衛矛科植物(Celastraceae)-福建賽衛矛(M. fokienensis)葉部、莖部和日本賽衛矛(M. japonica)莖部化學成分分離及活性之研究。從福建賽衛矛葉部得到十四個化合物,分別為七個ursane-type triterpenoids、二個oleanane-type triterpenoids、二個lupane-type triterpenoids、二個phenols及一個benzenoid;從莖部得到三十三個化合物,分別為十個ursane-type triterpenoids、九個oleanane-type triterpenoids、十三個lupane-type triterpenoids及一個agarofuran sesquiterpenoid。從日本賽衛矛莖部得到十五個化合物,分別為八個ursane-type triterpenoids、一個oleanane-type triterpenoid和六個agarofuran sesquiterpenoids。本研究共分離得到二十七個新化合物。
將化合物進行細胞毒殺活性篩選測試,其中活性化合物FL-3對於HepG2和Hep3B等細胞株具有明顯的細胞毒殺活性,其IC50值分別為3.8和4.5 ug/mL;FL-5對於HepG2細胞株也顯示細胞毒殺作用,其IC50值為4.6 ug/mL;FS-2對於HepG2、Hep3B、MDA-MB-231、MCF7、A549及HL 60具有顯著的細胞毒殺作用,其IC50值分別3.1、1.7、3.5、4.0、2.8和2.0 ug/mL;FS-6對於Hep3B、MCF7、Ca9-22及HL 60細胞株其細胞毒殺作用之IC50值分別為4.7、2.9、1.4和1.6 ug/mL。此外,進一步研究活性化合物FS-6 (28-hydroxy-3-oxo-lup-20(29)-en-30-al)針對HL 60細胞毒殺作用機轉。
In this study for bioactive compounds from Celastraceous plants, the extracts of the leaves and stems of M. fokienensis, as well as the stems of M. japonica were found to be cytotoxic and selected for fractionation. Up to now, 14 compounds were isolated form the leaves of M. fokienensis, including seven ursane-type triterpenoids, two oleanane-type triterpenoids, two lupane-type triterpenoids, two flavonoids and one benzenoid; 33 compounds were isolated form the stems of M. fokienensis, including ten ursane-type triterpenoids, nine oleanane-type triterpenoids, thirteen lupane-type triterpenoids and one agarofuran sesquiterpenoid; 15 compounds were isolated form the stems of M. japonica, including eight ursane-type triterpenoids, one oleanane-type triterpenoid, and six agarofuran sesquiterpenoids. Among them, 27 new compounds were isolated.
All triterpenoids were evaluated for their in vitro cytotoxicity toward human cancer cell lines. Among these compounds, FL-3 was found to be the most active toward the HepG2 and Hep3B cancer cell lines with IC50 of values 3.8 and 4.5 ug/mL, respectively; FL-5 was found to be active toward the HepG2 cancer cell lines with IC50 of values 4.6 ug/mL; FS-2 was found to be active toward the HepG2, Hep3B, MDA-MB-231, MCF7, A549 and HL 60 cancer cell lines with IC50 of values 3.1, 1.7, 3.5, 4.0, 2.8 and 2.0 ug/mL;FS-6 was found to be active toward the Hep3B、MCF7、Ca9-22 and HL 60 cancer cell lines with IC50 of values 4.7, 2.9, 1.4 and 1.6 ug/mL. The active compound, 28-hydroxy-3-oxo-lup-20(29)-en-30-al (FS-6), was selected for further mechanic investigation of survival suppression and proliferation of HL60 cells.
目錄-----------------------------------------------------Ⅰ
中文摘要-----------------------------------------------Ⅴ
英文摘要-----------------------------------------------Ⅶ
第一章 緒論----------------------------------------------1
第一節 前言---------------------------------------1
第二節 文獻回顧-----------------------------------4
第三節 植物型態及分佈----------------------------14
第四節 研究動機----------------------------------19
第二章 研究材料與方法-----------------------------------23
第三章 化合物之結構解析---------------------------------44
Ursane類化合物結構解析---------------------------44
第一節 microfokienoxane A (FL-1)之結構證明----------47
第二節microfokienoxane B (FL-2)之結構證明----------53
第三節microfokienoxane C (FL-3)之結構證明----------61
第四節3β,28-dihydroxy-11α-methoxyurs-12-ene (FL-5)結構鑑定---------------------------------------------69
第五節3β,16β-dihydroxyurs-11-oxours-12-ene (FS-16)結構鑑定---------------------------------------------76
第六節11α,12,16β-trihydroxy-3-oxours-12-ene (FS-17)結構鑑定--------------------------------------------85
第七節3β,12,16β-trihydroxy-11α-methoxyurs-12-ene (FS-20)之結構證明---------------------------------------94
第八節6β,12,23-trihydroxy-11α-methoxy-3-oxo-urs-12-ene (FS-29)之結構證明-------------------------------103
第九節1β,3β,28-trihydroxyurs-12-ene (FS-30)之結構證明------------------------------------------------113
第十節3β,12,23-trihydroxyurs-11-oxours-12-ene (FS-33)之結構證明------------------------------------------122
第十一節3β,16β-dihydroxy-11α-methoxyurs-12-ene (JS-1)之結構證明----------------------------------------130
第十二節12,23-dihydroxy-11α-methoxy-3-oxours-12-ene (JS-2)之結構證明---------------------------------138
第十三節3β,12-dihydroxy-11α-methoxyurs-12-en-23-al (JS-3)之結構證明--------------------------------------147
第十四節24-nor-6β,12-dihydroxy-11α-methoxy-3-oxours-12-
ene (JS-4)之結構證明-----------------------------157
第十五節13β,28-epoxy-23-hydroxy-3,12-dioxoursane (JS-5)之結構證明--------------------------------------167
第十六節13β,28-epoxy-3β-hydroxy-12-oxoursan-23-al (JS-6)之結構證明--------------------------------------175
第十七節13β,28-epoxy-16β-hydroxy-3-oxours-11-ene (JS-7)之結構證明--------------------------------------184
Oleanane類化合物結構解析------------------------192
第十八節 microfokienoxane D (FL-4)之結構證明------194
第十九節2,3-seco-11α,30-dihydroxyolean-12-en-2,3-dioic anhydride (FS-13)之結構證明-----------------------201
第二十節30-hydroxy-3,11-dioxoolean-12-ene (FS-21)之結構證明--------------------------------------------211
第二十一節1α,3β-dihydroxy-11-oxoolean-12-ene (FS-22)之結構證明----------------------------------------222
第二十二節30-hydroxy-3-oxoolean-12-ene (FS-31)之結構證明----------------------------------------------232
第二十三節3β,28-dihydroxy-1-oxoolean-18-ene (FS-32)之結構證明------------------------------------------241
第二十四節 2,3-seco-28-hydroxyolean-12-ene-2,3-dioic acid 3-methyl ester (JS-8)之結構證明---------------------251
Lupane類化合物結構解析--------------------------259
第二十五節7β-senecioyl-3-epi-betulinic acid (FS-11)之結構證明--------------------------------------------261
第二十六節7β-hydroxymethyl betulinate (FS-4)之結構證明------------------------------------------------268
第二十七節2,3-seco-30-hydroxylup-20(29)-ene-2,3-dioic acid (FS-7)之結構證明--------------------------------275
第四章 生物活性試驗------------------------------------282
第五章 結論--------------------------------------------284
第六章 相關實驗部分------------------------------------288
第一節 儀器與材料-------------------------------288
第二節 植物材料與分離純化-----------------------290
第三節 生物活性試驗-----------------------------301
第四節 各化合物之物理與光譜數據總整理-----------302
第七章 參考文獻----------------------------------------385
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