黑星紫金牛莖部之化學成分及細胞毒活性之研究

Chemical Constituents and Cytotoxicites from the Stem of Ardisia virens

林宜如(Yi-Ju Lin)

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(2006年)

https://doi.org/10.6832/KMU.2006.00020

摘要

中文摘要

黑星紫金牛(Ardisia virens Kurz.)，為小灌木, 屬紫金牛科，紫金牛屬植物。分布於印度、印尼、馬來西亞、泰國、越南、中國大陸及台灣。
其莖部之甲醇抽取物呈細胞毒性，將其進行分配萃取，得到正己烷、乙酸乙酯及水層共三層。針對三種癌細胞株(MCF-7, NCI-H460與SF-268) 細胞毒測試，確認活性層為正己烷層。此活性層進行矽膠管柱層析，得14個分畫，將活性分畫利用層析法分離，得34個化合物，其中共6個為新化合物分別為：1-(3-hydroxy-5-methoxyphenyl)pentan-1-one (1), 4- hydroxy-2-methoxy-6-pentadecylphenyl acetate (13), 4-hydroxy-2-meth- oxy-6-tridecylphenyl acetate (14), 6-(2’-acetoxytridecyl)-4-hydroxy-2- methoxyphenyl acetate (16), 6-(2’-acetoxypentadecyl)-4-hydroxy-2-meth- oxyphenyl acetate (17), 1-(2-formyl-3,6-dihydroxy-5-methoxyphenyl)- tridecan-2-yl-acetate (18), 一個為天然首次分離:1-(3,5-dihydroxyphenyl)- pentadecan-1-one (4)，已知化合物26個分別為1-(3,5-dihydroxyphenyl)- heptan-1-one ( 2 ), 1-(3,5-dihydroxyphenyl)nonan-1-one ( 3 ), olivetol ( 5 ), 5-heptylresorcinol ( 6 ), 5-nonylresorcinol ( 7 ), (+)-3-(2’S-hydroxytridecyl)- 5-methoxyphenol ( 8 ), (+)-3-(2’S-hydroxypentadecyl)-5-methoxyphenol (9), virenol A (10), virenol B (11), virenol C (12), ardisianol (15), ardisianone (19), cornudentanone (20), 6-(2-acetoxytridecyl)-5-hydroxy-2-methoxy-1,4- benzoquinone (21), 6-(2-acetoxypentadecyl)-5-hydroxy-2-methoxy-1,4- benzoquinone (22), 2-methoxy-6-tridecyl-1,4-benzoquinone (23), 2- methoxy-6-pentadecyl-1,4-benzoquinone ( 24 ), 5-O-methylrapanone ( 25 ), β-sitosterol ( 26 )與stigmasterol ( 27 )之混合物, linoleic acid ( 28 ) 與 stearic acid ( 29 )之混合物, palmitic acid ( 30 ), pentadecanoic acid ( 31 ), tetradecanoic acid ( 32 ), tridecanoic acid ( 33 ), 與octanoic acid ( 34 )之混合物。以上化合物之結構式皆以光譜分析決定。
分離的化合物中，以4-hydroxy-2-methoxy-6-pentadecylphenyl acetate (13),4-hydroxy-2-methoxy-6-tridecylphenyl acetate (14) 與ardisianol (15)針對這三種癌細胞株(MCF-7, NCI-H460與SF-268)均有細胞毒殺作用，活性分別為MCF-7 (IC50= 3.4, 2.6, 3.1 μg /ml), NCI-H460 (IC50= 0.1, 0.7, 0.6 μg /ml) and SF-268 (IC50= 2.7, 1.6, 2.6 μg /ml )，而化合物6-(2’-acetoxytridecyl)-4-hydroxy-2-methoxyphenyl acetate (16), ardisianone (19) 與cornudentanone (20) 選擇性的對NCI-H460癌細胞株有細胞毒殺作用，活性分別為 (IC50= 2.4, 2.3, 2.5 μg /ml)。

關鍵字

黑星紫金牛 ； 化學成分 ； 細胞毒活性 ； 陳益昇 ； 林宜如

並列摘要

Abstract
Ardisia virens Kurz. (Myrsinaceae) is a shrub, distributed in India, Indonesia, Malaysia, Thailand, Vietnam, China, and Taiwan. The methanolic extract of the stem of this species has shown cytotoxicity on high-throughput screening against MCF-7, NCI-H460 and SF-268 cancer cell lines and was partitioned into n-hexane, EtOAc and H2O-soluble layers. The n-hexane-soluble layer showed cytotoxicity against above three cancer cell lines. Investigation of the active n-hexane layer by column chromatography has led to the isolation of six new compounds: 1-(3-hydroxy-5-methoxyphenyl)pentan-1-one (1), 4-hydroxy-2-methoxy-6- pentadecylphenyl acetate (13), 4-hydroxy-2-methoxy-6-tridecylphenyl acetate (14), 6-(2’-acetoxytridecyl)-4-hydroxy-2-methoxyphenyl acetate (16), 6-(2’-acetoxypentadecyl)-4-hydroxy-2-methoxyphenyl acetate (17),, 1-(2-formyl-3,6-dihydroxy-5-methoxyphenyl)tridecan-2-yl acetate (18), one compound first isolated from plant origin：1-(3,5-dihydroxyphenyl)- pentadecan-1-one (4), together with twenty-seven known compounds：1-(3,5-dihydroxyphenyl)heptan-1-one (2), 1-(3,5-dihydroxyphenyl)nonan-1- one (3), olivetol (5), 5-heptylresorcinol (6), 5-nonylresorcinol (7), (+)-3- (2’S-hydroxytridecyl)-5-methoxyphenol (8), (+)-3-(2’S-hydroxypentadecyl)- 5-methoxyphenol (9), virenol A (10), virenol B (11), virenol C (12), ardisianol (15), ardisianone (19), cornudentanone (20), 6-(2-acetoxy- tridecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (21), 6-(2-acetoxy- pentadecyl)-5-hydroxy-2-methoxy-1,4-benzoquinone (22), 2-methoxy- 6-tridecyl-1,4-benzoquinone (23), 2-methoxy-6-pentadecyl-1,4-benzo- quinone (24), 5-O-methylrapanone (25), mixture of β-sitosterol (26) and stigmasterol (27), mixture of linoleic acid (28) and stearic acid (29), mixture of palmitic acid (30), pentadecanoic acid (31), tetradecanoic acid (32), tridecanoic acid (33), and octanoic acid (34).The structures of these compounds were elucidated by spectral analysis.
Among the isolates, 4-hydroxy-2-methoxy-6-pentadecylphenyl acetate (13), 4-hydroxy-2-methoxy-6-tridecylphenyl acetate (14), and ardisianol (15) showed cytotoxicities against MCF-7 (IC50= 3.4, 2.6, 3.1 μg /ml), NCI-H460 (IC50= 0.1, 0.7, 0.6 μg /ml) and SF-268 (IC50= 2.7, 1.6, 2.6 μg /ml ) cancer cell lines. respectively and 6-(2’-acetoxytridecyl)-4-hydroxy-2-methoxy- phenyl acetate (16), ardisianone (19) 與cornudentanone (20) showed selectively cytotoxicities only against NCI-H460 (IC50= 2.4, 2.3, 2.5 μg /ml)cancer cell lines respectively.

並列關鍵字

Ardisia virens Kurz ； Myrsinaceae ； MCF-7 ； NCI-H460 ； SF-268 ； ardisianone ； cornudentanone ； Yi-Ju Lin ； Ih-Sheng Chen

參考文獻

第九章、參考文獻

1. Lu SY, Yang YP. Myrsinaceae in Flora of Taiwan. 2nd. ed. Editorial Committee of the Flora of Taiwan: Taipei, 1998; Vol. IV, pp 40-56

2. Chinese Bencao, Editorial Committee of Chinese Bencao, Shanghai Science and Technology Press, Shanghai. 1999; Vol. 6, pp 73-4

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

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