- 學位論文
天然活性藥物探索—台灣產波羅蜜屬植物猴面果及馬來波羅蜜；福木屬植物福木之生物活性成分研究
Bioactive Constituents Discovery in Formosan Moraceae Plants, Artocarpus rigida, Artocarpus elasticus, and Guttiferae Plant, Garcinia subelliptica
摘要
利用光譜學的方法，一個含有oxepine環取代的新骨架化合物artocarpol I (1)自波羅蜜屬植物猴面果(Artocarpus rigida)被分離出；同時也分離出一個具有biphenylpropanoid骨架的新化合物artocarpol J (2)。Artocarpol I (1) 及 artocarpol J peracetate (3)對於中性球(neutrophil)中由formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB)誘導產生超氧陰離子(superoxide anion formation)具有強烈的濃度依存性(concentration-dependent manner)抑制，其IC50 值分別為17.1 + 0.40 及20.5 + 2.60 ???翩C藉由已分離之stilbene衍生物可推斷，此一系列新骨架酚性化合物是由stilbene類衍生物生合成而得。 台產馬來波羅蜜(Artocarpus elasticus)根皮部的成份研究中，分離出5個新的黃酮類衍生物分別命名為artelastoheterol (4), artelasticinol (5), cycloartelastoxanthone (6), artelastoxanthone (7), cycloartelastoxanthendiol (8)，及已知黃酮類衍生物artonols A (9)及 B (10), artonin F (11), cudraflavone B (12), cycloartobiloxanthone (13), cyclomorusin (14)，化合物4-8的結構鑑定是依據光譜學的方法及比對相關文獻資料而得；同時化合物artonol A (9)對於A549 human cancer cell line具有細胞毒性，其IC50 值為 1.1 ?慊/mL，其餘化合物之抗發炎活性篩選正在進行中。 關於金絲桃科植物福木(Garcinia subelliptica)，此次進行心材成分的研究，共分離出Garcinielliptones HA (15), HC (17)及 HF (20)三個未曾發表的萜類新骨架，同時分離出garcinielliptones HB (16), HD (18)及 HE (19)三個具有phloroglucinol骨架的新化合物，及2,6-dihydroxy-1,5-dimethoxyxanthone (21), 3,5-dihydroxy-4-mehoxy xanthone (22), 1,5-dihydroxyxanthone (23), 1,7-dihydroxyxanthone (24) 四個已知xanthone類衍生物。結構鑑定則是利用光譜學的方法及比對相關文獻資料。 利用agarose gel電泳及pBR322 DNA，具有超螺旋纏繞結構的環狀DNA，可以用來測定15-20誘導DNA斷裂活性。在銅離子Cu (II)存在的情況下，化合物17及18造成超螺旋質體pBR322顯著的斷裂；在化合物17-Cu (II)-誘導 DNA 斷裂實驗中，利用Cu (I)-專一性螯合劑neocuproine的加入可顯示Cu (I)是必須的中間體，而在化合物18-Cu (II)-誘導 DNA 斷裂實驗中，利用同樣的螯合劑顯示出Cu (I)中間體則是非必須的。 在化合物17-Cu (II)-誘導 DNA 斷裂實驗中，藉由加入catalase產生的抑制效果及加入KI及superoxide dismutase所產生的結果，顯示活性氧H2O2 及 O2·-有參與反應。
並列摘要
From the root bark of Artocarpus rigida, a novel phenolic compound containing an oxepine ring, artocarpol I (1) and a new biphenylpropanoid, artocarpol J (2) were isolated. The structures including relative configurations were elucidated by spectroscopic data. Artocarpol I (1) and artocarpol J peracetate (3) strongly inhibited in a concentration-dependent manner the formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB)–stimulated superoxide anion formation in neutrophils with IC50 values of 17.1 + 0.40 and 20.5 + 2.60 ????, respectively. Biogenetically all the novel phenolic compounds isolated from this plant seem to be derived from stilbene. From the root bark of Artocarpus elasticus, five new prenylated flavonoids, artelastoheterol (4), artelasticinol (5), cycloartelastoxathone (6), artelastoxanthoe (7), and cycloartelastoxanthendiol (8), along with five known compounds, were isolated. The structures of 4-8 were elucidated by spectroscopic methods and through comparison with data reported in the literature. The preciously known compound, artonol A (9), exhibited cytotoxic activity against the A549 human cancer cell line, with an ED50 value of 1.1 ?慊/mL. From the heartwood of Garcinia subelliptica, Garcinielliptones HA (15), HC (17), and HF (20), possessing unprecedented terpenoid skeleton, along with three new terpenoids, garcinielliptones HB (16), HD (18), and HE (19) were established by extensive analysis of spectroscopic data. The ability of 15-20 to induce DNA-cleavage activity was examined using pBR322, a supercoiled, covalently closed circular DNA, and analyzed by agarose gel electrophoresis. In the present of Cu (II), compounds 17 and 18 caused significant breakage of supercoiled plasmid pBR322. The products were relaxed circles with no detectable linear forms. In the Cu (II)-mediated DNA damage of 17, Cu (I) was shown to be an essential intermediate by using the Cu (I)-specific sequestering reagent neocuproine. In the Cu (II)-mediated DNA damage of 18, Cu (I) was not shown to be an essential intermediate by using the same Cu (I)-specific sequestering reagent. The involvement of active oxygen species, H2O2 and O2·- in the 17-Cu (II)-mediated breakage reaction, was established by the inhibition of DNA damage by catalase and revealed DNA breakage by KI and superoxide dismutase.