Epicoccum sorghinum 之活性天然產物

Bioactive Natural Products from Epicoccum sorghinum

張靜佳(Ching-Chia Chang)

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(2019年)

摘要

本論文之附球菌 Epicoccum sorghinum (Sacc.) Aveskamp，為蘆竹 Arundo donax Linn. 莖部所分離培養出內生真菌。經篩選發現其乙酸乙酯層粗萃物具有抗發炎與細胞毒殺活性，因此將 Epicoccum sorghinum 之乙酸乙酯粗萃物利用生物活性導向分離法 (bioassay-guided fractionation) 純化分離出一個新化合物，並命名為 epicorepoxydon A (1)，以及六個已知 benzyl 骨架衍生物化合物 (2–7)，一個已知 ethyl phenyl 骨架衍生物化合物 (8)，七個已知 diketopiperazine 化合物 (9–15) 及一個 steroid 化合物 (16)。其化合物之結構鑑定，主要經由核磁共振光譜 (NMR)、質譜 (MS) 等數據來確定其結構。新化合物的相對構型是藉由 NOESY 圖譜來確定的，而絕對構型主要利用 X-ray 單晶繞射圖來確定其立體。
同時將 E. sorghinum 所分離出來之化合物進行活性測試，其實驗結果顯示化合物2與6同時具有抑制人類乳癌細胞 (MDA-MB-231)、肝癌細胞 (HepG2) 以及肺癌細胞 (A549)活性，化合物4與6顯示出具有抗發炎活性，化合物2具有抗血小板凝集活性，化合物2與6具有抗血管新生活性及化合物4, 5, 6和8具有自由基清除之活性。
另外更進一步將本論文所分離出一系列化合物進行生物合成之推測，並利用其結構與活性關係 (Structure-Activity Relationship) 進行研究與探討。

關鍵字

附球菌 ； 蘆竹 ； 自由基清除 ； 細胞毒殺 ； 抗發炎活性 ； 抗血小板凝集活性 ； 抗血管新生活性

並列摘要

In the current research, the subject endophyte Epicoccum sorghinum (Sacc.) Aveskamp was isolated from the stem of Arundo donax Linn. Its ethyl acetate extract was exhibited anti-inflammatory and cytotoxic activity. One new compound, named as epicorepoxydon A (1), together with six known benzyl-skeleton derivatives (2–7), one known ethyl phenyl-skeleton derivative (8), seven known diketopiperazines (9–15), and one known steroid (16) were discovered by bioassay-guide fractionation. The structures of isolates were established by spectroscopic data, such as NMR and MS spectra. The relative configuration of compound 1 was determined by the NOESY spectrum. Moreover, the absolute configuration was deduced by X-ray single crystal analysis.
Additionally, all isolates were evaluated various bioactivity assays, including cytotoxicity, anti-inflammatory, anti-platelet aggregation, anti-angiogenesis and free radical scavenging activities. Compounds 2 and 6 demonstrated cytotoxic activity against three human cancer cell lines (MDA-MB-231, HepG2, and A549). Compounds 4 and 6 showed anti-inflammatory activity. Compound 2 possessed anti-platelet aggregation activity. Compounds 2 and 6 exhibited anti-angiogenesis activity. And compounds 4, 5, 6 and 8 had free radical scavenging activity.
Furthermore, we proposed a biosynthesis pathway of polyketide secondary metabolites and investigated their structure-activity relationship (SAR) of key isolates from this fungus.

並列關鍵字

Epicoccum sorghinum ； Arundo donax ； free radical scavenging activity ； cytotoxic activity ； anti-inflammatory activity ； anti-platelet aggregation activity ； anti-angiogenic activity.

參考文獻

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