海綿Theonella sp.二次代謝物與生物活性的研究

Studies on the secondary metabolites and biological activities from a marine sponge Theonella sp.

孫藝龍(Yi-Long Sun)

指導教授 ： 石明正

共同指導教授 ： 黃鈺婷 ； 蘇瑞欣(Jui-Hsin Su)

義守大學/醫學院/生物科技學系/碩士(2014年)

https://doi.org/10.6343/ISU.2014.00326

摘要

在先前的研究中，海綿被認為是具有潛在活性天然物豐富來源的生物。到目前為止，有三個治療藥物（兩個抗癌和一個抗病毒藥物）從海綿中獲得。為了找尋具有生物活性的代謝產物，我們從一種海綿Theonella sp. 的乙酸乙酯萃取物進行化學成分的研究。本研究分離出 7 個天然化合物 (1–7) ，其中包括 4 個 4-methylene 固醇類化合物 (1–4) 及兩個核苷類化合物 (5和6) 和一個大環內酯類化合物 (7)。除了已知的化合物 2–4 及 6 和 7，acetyltheonellasterol F (1) 為一個新的化合物，而 5'-O-acetyl-2'-deoxyuridine (5) 被發現為一個新的天然產物。這些化合物的結構是根據光譜數據的基礎上進行鑑定。
化合物 1–7 針對人類乳癌細胞 (MCF-7 and MDA-MB-231)、依賴荷爾蒙乳癌細胞 (T-47D)、人類結腸癌細胞 (HCT-116和DLD-1)、人類慢性骨髓性白血球癌細胞 (K562) 和人類T淋巴母細胞，急性淋巴細胞性白血病 (Molt 4) 進行毒殺試驗。結果顯示化合物 7 在所有測試化合物中對 6 種癌細胞 MCF-7、T47D、HCT -116、DLD- 1、K562 和 Molt 4 的細胞毒殺活性最好其 IC50 值分別為 1.03、0.65、0.78、0.55、0.01和 0.02 μg/mL。在抗氧化活性測試方面，化合物1–7均無抗氧化活性。

關鍵字

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並列摘要

In previous study, marine sponges have been found to be a rich source of potential bioactive natural products. To date, there are three therapeutic agents (two anticancer and one antiviral) that derive from the marine sponges. In order to search for bioactive metabolites, we have studied the chemical constituents from the EtOAc extract of a sponge Theonella sp. This study had led to the isolation of seven natural compounds 1–7, including four 4-methylene sterols (1–4), two nucleosides (5 and 6) and one macrolide (7). Except for the known compounds 2–4, 6 and 7, the acetyltheonellasterol F (1) was obtained as a new compound, while 5'-O-acetyl-2'-deoxyuridine (5) was found to be new natural product. The structures of these compounds were elucidated on the basis of their spectroscopic data.
The cytotoxicity of compounds 1–7 against the MCF-7 and MDA-MB-231 (human breast adenocarcinoma), T-47D (human hormone-dependent breast cancer), HCT-116 and DLD-1 (human colon adenocarcinoma), K562 (human chronic myelogenous leukemia) and Molt 4 (human T lymphoblast, acute lymphoblastic leukemia) tumor cell lines were determined. The results showed that compound 7, the most potent of compounds 1–7, exhibited cytotoxicity against MCF-7, T47D, HCT-116, DLD-1, K562 and Molt 4, with IC50s of 1.03, 0.65, 0.78, 0.55, 0.01 and 0.02 μg/mL, respectively. Furthermore, the antioxidant activity of compounds 1–7 was also tested. The results showed that compounds 1–7 have been shown to be not antioxidant activity.

並列關鍵字

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