台灣馬鞍樹莖部化學成分及細胞毒活性之研究

台灣馬鞍樹（Maackia taiwanensis Hoshi & Ohashi）又名台灣島槐，為台灣固有種，屬於豆科馬鞍樹屬的落葉性喬木，高可達10公尺，小枝呈棕綠色，分布於陽明山國家公園和屏東縣。其莖部之甲醇抽取物對MCF-7具有細胞毒活性，將其進行分配萃取，得到乙酸乙酯層、正丁醇層及水層，共三個可溶部的抽出物。針對三種癌細胞株(MCF-7, NCI-H460與SF-268) 進行細胞毒測試，確定活性層為乙酸乙酯層。將乙酸乙酯層進行矽膠管柱層析，共分得50個化合物，包括36個flavonoid類化合物為：(-)-maackicarpin (1), (-)-O-3’-secomaackicarpin (2), (-)-3-hydroxy-2,9-dimethoxypterocarpan (3), (-)-medicarpin (4), (-)-secundiflorol I (5), (-)-3,9-dihydroxypterocarpan (6), (-)-vesticarpan (7), (-)-2-hydroxymaackiain (8), (-)-maackiain (9), (-)-isoneorautenol (10), (-)-11b-hydroxy-11b,l- dihydromedicarpin (11), 2’,4’-dihydroxychalcone (12), 4,2’,4’-tridihydroxychalcone (13), (+)-ferreirin (14), (-)-4’,5,7-trihydroxyisoflavanone (15), 2’,4’- dihydroxydihydrochalcone (16), ?v?y?w?{??,2',4'-trihydroxy-4-methoxydihydrochalcone (17), (+?y)-1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4’-hydroxyphenyl)- 1-propanone (18), (+)-7-methoxy-flavan-3,4-diol (19), (-)-trans-3-hydroxy-7-methoxyflavanone (20), (-)-isobavachin (21), (-)-5-hydroxysophoranone (22), (+)-7-O-methylvestitol (23), (+)-4’-hydroxy-7-methoxyisoflavan (24), (-)- liquiritigenin (25), warangalone (26), osajin (27), formononetin (28), genistein (29), 8-???z?莙imethylallydaidzein (30), orobol (31), 2’,4’,7-trihydroxyisoflavone (32), 3’,4’,7-trihydroxyisoflavone (33), 3’-hydroxyformononetin (34), biochanin A (35)和2’-hydroxyformonetin (36)；7個苯環類化合物: trans-methyl ferulate (37), methyl 3-(3,4-dimethoxyphenyl)propenoate (38), methyl 3-(3,4,5-trimethoxyphenyl)acrylate (39), 4-hydroxybenzaldehyde (40), 4-hydroxybenzoic acid (41), vanillin (42)和syringaldehyde (43)；3個三萜類化合物：lupeol (44), 混合物(24R)-6??-hydroxystigmasta-4-en-3-one (47) 和(22E,24S)-6??-hydroxystigmasta-4,22-dien-3-one (48)；2個固醇類化合物：混合物 ??-sitosterol (45) 和stigmasterol (46); 2個lignan： (?b)-syringaresinol(49)及(-)-balanophonin (50)。以上化合物之結構皆以光譜分析決定。所有分離得到的化合物中，化合物1與2為新化合物；在細胞毒活性h方面：(-)-maackicarpin (1), (-)-maackiain (9), warangalone (26)和osajin (27) 在50μM對於MCF-7癌細胞呈現抑制作用；(-)-maackicarpin (1),(-)-O-3’-secomaackicarpin (2), (-)-3-hydroxy-2,9-dimethoxypterocarpan (3),(-)-medicarpin (4), (-)-3,9-dihydroxypterocarpan (6), (-)-vesticarpan (7), (-)-2-hydroxymaackiain (8), (-)-maackiain (9), 2’,4’-dihydroxychalcone (12), isoliquiritigenin (13), (+)-4’-hydroxy-7-methoxyisoflavan (24), warangalone (26), osajin (27) 和genistein (29)在50μM對於NCI-H460癌細胞呈現抑制作用；(-)-maackicarpin (1)和isoliquiritigenin (13)無論是在高濃度或是低濃度均對NCI-H460癌細胞呈現顯著抑制作用：(-)-maackicarpin (1), (-)-O-3’-secomaackicarpin (2), (-)-3-hydroxy-2,9-dimethoxypterocarpan (3), (-)-medicarpin (4), (-)-3,9-dihydroxypterocarpan (6), (-)-maackiain (9), 2’,4’-dihydroxychalcone (12), isoliquiritigenin (13), warangalone (26)和osajin (27) 在高濃度50μM對於SF-268癌細胞呈現細胞毒殺的活性；綜合上述幾點，化合物(-)-maackicarpin (1), (-)-maackiain (9), warangalone (26)和osajin (27) 在高濃度50μM的時候對三種癌細胞株MCF-7, SF-268, NCI-H460均呈現有意義的細胞毒殺作用。將所分離得到的化合物進一步進行IC50毒性分析，發現(-)-maackicarpin (1), (-)-medicarpin (4), 2’,4’-dihydroxychalcone (12),isoliquiritigenin (13)和osajin (27)對MCF-7, NCI-H460及SF-268三種細胞株呈現邊緣細胞毒活性。

關鍵字

台灣馬鞍樹,細胞毒活性,化學成分

並列摘要

Maackia taiwanensis Hoshi & Ohashi (Leguminosae) is a deciduous tree, endemic in Taiwan, up to 10 m high with greenish brown branchlets,distributed in Yangmingshan National Park and recently also found in Pingtung County. It has another common name, “Taiwan Dao-Huai”. The MeOH extract of the stem of this plant has shown cytotoxicity on high-throughput screening against MCF-7 cancer cell line and was partitioned into EtOAc, n-BuOH and H2O-soluble layers. The EtOAc-soluble layer showed cytotoxicity against MCF-7, NCI-H460 and SF-268 cancer cell lines. Investigation of the active EtOAc-soluble layer by column chromatography has led to the isolation of fifty compounds, including thirty-six flavonoids: (-)-maackicarpin (1), (-)-O-3’-secomaackicarpin (2), (-)-3-hydroxy-2,9-dimethoxypterocarpan (3), (-)-medicarpin (4), (-)-secundiflorol I (5), (-)-3,9-dihydroxypterocarpan (6), (-)-vesticarpan (7), (-)-2-hydroxymaackiain (8), (-)-maackiain (9), (-)-isoneorautenol (10), (-)-11b-hydroxy-11b,l-dihydromedicarpin (11), 2’,4’-dihydroxychalcone (12), isoliquiritigenin (13), (+)-ferreirin (14), (-)-4’,5,7-trihydroxyisoflavanone (15), 2’,4’-dihydroxy- dihydrochalcone (16), ?v?y?w?{??,2',4'-trihydroxy-4-methoxydihydrochalcone (17), (+?y)-1-(2,4-dihydroxyphenyl)-3-hydroxy-3-(4’-hydroxyphenyl)-1-propanone (18), (+)-7-methoxyflavan-3,4-diol (19), (-)-trans-3-hydroxy-7-methoxy- flavanone (20), (-)-isobavachin (21), (-)-5-hydroxysophoranone (22), (+)-7-O-methylvestitol (23), (+)-4’-hydroxy-7-methoxyisoflavan (24), (-)- liquiritigenin (25), warangalone (26), osajin (27), formononetin (28), genistein (29), 8-???z???{dimethylallydaidzein (30), orobol (31), 2’,4’,7-trihydroxyisoflavone (32), 3’,4’,7-trihydroxyisoflavone (33), 3’-hydroxyformononetin (34), biochanin A (35) and 2’-hydroxyformonetin (36); seven benzenoids: trans-methyl ferulate (37), methyl 3-(3,4-dimethoxyphenyl)propenoate (38), methyl 3-(3,4,5-trimethoxyphenyl)acrylate (39), 4-hydroxybenzaldehyde (40), 4-hydroxybenzoic acid (41), vanillin (42) and syringaldehyde (43); three terpenoids: lupeol (44), a mixture of (24R)-6??-hydroxystigmasta-4-en-3-one (47) and (22E,24S)-6??-hydroxystigmasta-4,22-dien-3-one (48); two steroids: a mixture of ??-sitosterol (45) and stigmasterol (46); two lignan: (?b)-syringaresinol (49) and (-)-balanophonin (50). The structures of these compounds were elucidated by spectral analysis. Among the isolates, compounds 1 and 2 are new compounds. Compounds 1, 9, 26 and 27 showed cytotoxicities against MCF-7 cancer cell lines at 50μM；compounds 1, 2, 3, 4, 6, 7, 8, 9, 12, 13, 24, 26, 27 and 29 showed cytotoxicities against NCI-H460 cancer cell lines at 50μM；compounds 1 and 13 whatever at 10μM or 50μM both showed cytotoxicities against NCI-H460 cancer cell lines；compounds 1, 2, 3, 4, 6, 9, 12, 13, 26 and 27 showed cytotoxicities against SF-268 cancer cell lines at 50μM. Accroding to the above results, compounds 1, 9, 26 and 27 showed cytotoxicities against MCF-7,NCI-H460 and SF-268 cancer cell lines at 50μM. According to these data, compounds 1, 4, 12, 13, 27 show marginal cytotoxic activity against NCI-H460 and SF-268 cell lines.