高士佛紫金牛之化學成分及生物活性之研究

Chemical Constituents and Bioactivities from Ardisia kusukuensis

蘇昭禎(Chao-Chen Su)

指導教授 ： 陳益昇

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2008年)

摘要

高士佛紫金牛為紫金牛科（Myrsinaceae）紫金牛屬（Ardisia）之小型亞灌木，植株高約20公分，為台灣固有種植物，分布於恆春半島八百公尺以下山區。持續研究台灣產植物之活性成分，發現該植物全草之甲醇抽出物對於MCF-7、NCI-460與SF-268等三株癌細胞具有細胞毒活性與抗結核菌活性。將該植物全株之甲醇抽出物經由分配得到正己烷層、乙酸乙酯層與水層。正己烷層和乙酸乙酯層對於MCF-7、NCI-460與SF-268等三株癌細胞顯示出強細胞毒活性。乙酸乙酯層對Mycobacterium tuberculosis H37RV具有抗結核菌活性。
正己烷層和乙酸乙酯層經由化學研究分離得到六個新的alkenyl resorcinols類化合物： kusukuenol A1 (1), kusukuenol A2 (2), kusukuenol B1 (3), kusukuenol B2 (4), kusukuenol C1 (5) 和kusukuenol C2 (6)，與二十一個已知化合物：包括六個alkenyl resorcinols類化合物：5-(8'Z-heptadecenyl)resorcinol (7), 5-(8'Z-pentadecenyl)resorcinol (8), 2-methyl-5-(8'Z-heptadecenyl)resorcinol (9), 2-methyl-5-(8'Z-pentadecenyl)resorcinol (10), oncostemonol D (11), dehydrobis- gravillol (12)；三個alkyl resorcinols類化合物： bisgravillol (13), 1-(3,5- dihydroxyphenyl)heptan-1-one (14)和1-(3,5-dihydroxyphenyl)nonan-1-one (15)；兩個benzoquinones類化合物：ardisianone (16) 和cornudentanone (17)；兩個benzenoid類化合物：4-hydroxybenzoic acid (18) 和hydroquinone (19)；兩個chlorophylls類化合物：pheophytin-a (20) 和132-hydroxy-(132-S)- pheophytin-a (21)；五個steroids類化合物：??-spinasterol (22), ??-sitosterol (23)及stigmasterol (24) 之混合物, 6??-hydroxystigmasta-4-en-3-one (25),6??- hydroxy-stigmasta-4,22-dien-3-one (26),及6??-hydroxycampest-4-en-3-one (27) 之混合物。以上化合物之結構經由各種光譜分析及化學衍生予以確認。
所有分離得到的化合物中，化合物8顯示對於SF-268癌細胞株呈現邊緣細胞毒殺活性；化合物15與16顯示選擇性的對於NCI-H460癌細胞株呈現細胞毒殺活性。化合物2, 7, 8, 10, 15與 19顯示具有抗結核菌之活性。

關鍵字

高士佛紫金牛 ； 紫金牛科 ； 全草 ； 細胞毒活性 ； 抗結核活性

並列摘要

Ardisia kusukuensis Hay. (Myrsinaceae) is an endemic suffrutescent subshrubs to 20 cm tall, distributes in forests below 800 m of the Hengchun Peninsula in Taiwan. As an extension of our continuing studies on the active constituents of Formosan plants. The methanolic extract of the whole plant of this species showed cytotoxic activity against MCF-7, NCI-H460 and SF-268 cancer cell lines and antitubercular activity against Mycobacterium tuberculosis H37RV in vitro. The methanolic extract of the whole plant was partitioned into n-hexane, EtOAc, and H2O-soluble layers. The n-hexane and EtOAc-soluble layers showed potent cytotoxicity against MCF-7, NCI-H460 and SF-268 cancer cell lines. The EtOAc-soluble layer showed antitubercular activity.
Investigation of the n-hexane and EtOAc-soluble layers led to the isolation of six new alkenyl resorcinols: kusukuenol A1 (1), kusukuenol A2 (2), kusukuenol B1 (3), kusukuenol B2 (4), kusukuenol C1 (5) and kusukuenol C2 (6), along with twenty-one known compounds: including six alkenyl resorcinols: 5-(8'Z-hepta- decenyl)resorcinol (7), 5-(8'Z-pentadecenyl)resorcinol (8), 2-methyl-5-(8'Z- heptadecenyl)resorcinol (9), 2-methyl-5-(8'Z-pentadecenyl)resorcinol (10), oncostemonol D (11), dehydrobisgravillol (12), three alkyl resorcinols: bisgravillol (13), 1-(3,5-dihydroxyphenyl)nonan-1-one (14) and 1-(3,5-dihydroxy- phenyl)heptan-1-one (15), two benzoquinones: ardisianone (16) and cornudentan- one (17), , two benzenoids: 4-hydroxybenzoic acid (18) and hydroquinone (19), two chlorophylls: pheophytin-a (20) and 132-hydroxy-(132-S)-pheophytin-a (21), six steroids: ??-spinasterol (22), a mixture of ??-sitosterol (23) and stigmasterol (24), a mixture of 6??-hydroxystigmasta-4-en-3-one (25), 6??-hydroxystigmasta- 4,22-dien- 3-one (26), and 6??-hydroxycampest-4-en-3-one (27). The structures of these compounds were determined by spectroscopic analysis and chemical derivation.
Among these isolates, compound 8 showed marginal cytotoxic activity against SF-268 cancer cell line, compounds 16 and 17 showed selectively cytotoxic activity against NCI-H460 cancer cell line. Compounds 2, 7, 8, 10, 15 and 19 showed antitubercular activities against M. tuberculosis H37RV in vitro.

並列關鍵字

Ardisia kusukuensis ； Myrsinaceae ； whole herb ； kusukuenol ； resorcinol ； cytotoxic activity ； antitubercular activity

參考文獻

第九章、 參考文獻

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2. Health and National Health Insurance Annual Statistics Information Service http://www.doh.gov.tw/statistic/index.htm

3. Tian Z, Chang MN, Sandrino M, Huang L, Pan JX, Arison B, Smith J, Lam YKT. Quinones from Ardisia cornudentata. Phytochemistry 1987; 26: 2361-2

4. Ogawa H, Natori S. Hydroxybenzoquinones from Myrsinaceae plants. II. Distribution among Myrsinaceae plants in Japan. Phytochemistry 1968; 7: 773-82