布朗花燭衍生菌赭瓣麴黴菌之二次代謝產物及生物活性研究

Studies on the Secondary Metabolites and Bioactivities of Aspergillus ochraceopetaliformis Isolated from Anthurium brownii

楊代筠(Dai-Yun Yang)

指導教授 ： 張芳榮

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2017年)

摘要

本論文之赭瓣麴黴菌Aspergillus ochraceopetaliformis為由布朗花燭Anthurium brownii葉部所分離培養出的衍生真菌。經篩選發現其乙酸乙酯層具有抗發炎的活性，因此利用生物活性導向分離法(bioassay-guided fractionation)從赭瓣麴黴菌之乙酸乙酯萃取物中分離純化出五個新化合物並命名為asperochrapyran (1)和asperochralactones A‒D (2‒5)，以及十二個已知聚酮6‒17與四個已知環縮二氨酸18‒21。化合物之結構鑑定，主要經由核磁共振光譜(NMR)、質譜(MS)等數據而確定結構。新化合物的相對構型是藉由化合物的偶合常數與NOESY圖譜來確定的，而絕對構型則是由圓二色(Circular Dichroism, CD)光譜與電子圓二色(Electronic Circular Dichroism, ECD)光譜計算比較後而確定。利用上述方式也將已知化合物6的絕對立體定為5S,6R,8S,9R。另外，主要的聚酮化合物皆進行抗發炎與細胞毒殺活性測試。實驗結果顯示，化合物7對於人類肝癌細胞具有明顯的細胞毒殺活性(IC50 = 7.90 ± 0.06 μg/mL)，而化合物10則對於人類肺癌細胞(IC50 = 4.40 ± 0.29 μg/mL)、肝癌細胞(IC50 = 5.61 ± 0.04 μg/mL)及乳癌細胞(IC50 = 6.68 ± 0.02 μg/mL)皆具有顯著的細胞毒殺效果。然而，所有送測之化合物皆不具抗發炎活性。

關鍵字

布朗花燭 ； 赭瓣麴黴菌 ； 聚酮

並列摘要

In the current research, the subject endophyte Aspergillus ochraceopetaliformis Bat. & Maia (Trichocomaceae) was isolated and cultured from the leaves of Anthurium brownii Mast. (Araceae). The ethyl acetate layer was found to be active in anti-inflammatory assay. Five new compounds asperochrapyran (1) and asperochralactones A‒D (2‒5), together with twelve known polyketides 6‒17 and four known diketopiperazines 18‒21, were isolated by bioassay-guided fractionation from the active ethyl acetate layer. The structures of these compounds were determined by spectroscopic methods, such as NMR and MS technologies. The relative configurations of the new compounds were elucidated especially by the information of their proton-proton coupling constants and NOESY spectra. Furthermore, the absolute configurations were determined by circular dichroism (CD) and electronic circular dichroism (ECD) spectroscopic analyses. Using the abovementioned methods, the absolute configuration of 6 was determined to be 5S,6R,8S,9R. The major polyketides were selected and subjected to assays of anti-inflammatory and cytotoxic activities. Compound 7 showed strong cytotoxicity against HepG2 cell line, with an IC50 value of 7.90 ± 0.06 μg/mL. Also, compound 10 exhibited significant cytotoxicity against A549 (IC50 = 4.40 ± 0.29 μg/mL), HepG2 (IC50 = 5.61 ± 0.04 μg/mL), and MDA-MB-231 (IC50 = 6.68 ± 0.02 μg/mL) cell lines. However, all test compounds didn’t show anti-inflammatory activity.

並列關鍵字

Anthurium brownii ； Aspergillus ochraceopetaliformis ； Polykedtide

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