开口箭化学成分及抗肿瘤活性

doi:10.7503/cjcu20190167

摘要/Abstract

摘要：

从开口箭新鲜根茎中分离得到8个化合物, 通过理化性质分析、质谱、红外光谱及核磁共振波谱检测等方法鉴定了其结构, 分别为开口箭皂苷J(1)、 (25S)-26-O-β-D-吡喃葡萄糖基呋甾-1β,3β,22α,26-四羟基-3-O-β-D-吡喃葡萄糖苷(2)、洋地黄毒苷元-3-O-α-L-吡喃岩藻糖苷(3)、弯蕊皂苷元B(4)、异罗斯考皂苷元(5)、罗斯考皂苷元(6)、香豌豆酚(7)及(+)-儿茶素(8). 其中, 化合物1为新化合物, 化合物3, 4, 7和8为首次从该属植物中分离得到. 在抗人结肠癌细胞LoVo和胃癌细胞BGC-823活性评价中, 化合物5和6表现出较强的抗肿瘤活性, 半抑制浓度(IC₅₀)值分别达到0.532和0.757 μmol/L.

关键词: 开口箭, 化学成分, 抗肿瘤活性

Abstract:

Tupistra chinensis(Liliaceae), mainly distributed in southwestern China, is a rich source of steroidal sapogenins, saponins and flavans. These components exhibit diverse biological activities such as anti-inflammatory, anti-fungal and anti-tumor properties. As a part of a continuing study for the discovery of novel cytotoxic agents, eight compounds were isolated from the fresh rhizomes of Tupistra chinensis, and their structures were established on the basis of chemical methods and spectral data(MS, IR, NMR), including tupistroside J(1), (25S)-26-O-β-D-glucopyranosyl-furost-1β,3β,22α,26-tetraol-3-O-β-D-glucoside(2), digitoxigenin-3-O-α-L-fucopyranose(3), watti-genin B(4), epiruscogenin(5), epiruscogenin(6), orobol(7), (+)-catechin(8). Compound 1 was a new compound, and compounds 3, 4, 7 and 8 were isolated from Tupistra Ker-Gawl for the first time. All compounds were tested in vitro for their cytotoxic activities against the Human LoVo and BGC-823 cell lines, and compounds 5 and 6 were found to possess significant cytotoxicity against the tested tumor cell lines with half maximal inhibitory concentration(IC₅₀) values of 0.532 and 0.757 μmol/L, respectively.

Key words: Tupistra chinensis baker, Chemical constituent, Antitumor activity

中图分类号:

O629

TrendMD:

肖艳华, 张广杰, 宗良, 刘国宏, 任丽君, 董俊兴. 开口箭化学成分及抗肿瘤活性. 高等学校化学学报, 2019, 40(9): 1897.

XIAO Yanhua, ZHANG Guangjie, ZONG Liang, LIU Guohong, REN Lijun, DONG Junxing. Chemical Constituents and Antitumor Activity of Tupistra chinensis ^†. Chem. J. Chinese Universities, 2019, 40(9): 1897.

图/表 4

参考文献 30

[1]	Wu X., Fan J., Ouyang Z ., J. Pharmacol 2014, 66( 3), 453-465
[2]	Zhao H., Wang H. N., Xu H., ., Journal of Shanxi University of Technology(Natural Science Edition) 2013, 29, 62-69
	( 赵桦, 王慧娜, 徐皓 . 陕西理工学院学报自然科学版, 2013, 29, 62-69)
[3]	Huang W., Zhang H., Zou K ., Neoplasma, 2012, 59( 613-621
[4]	Xie J. Y., Zhang D. D., Li Y. Z ., Pharmacology and Clinics of Chinese Materia Medica, 2014, 30, 82-86
	( 谢锦艳, 张东东, 李玉泽 . 中药药理与临床, 2014, 30, 82-86)
[5]	Zou K., Wang J. Z., Guo Z. Y ., J. Magn. Reson Chem, 2009, 47( 87-91
[6]	Zou K., Wang J. Z., Wu J ., J. Chin. Chem Lett, 2007, 18( 1239-1242
[7]	Zou K., Wu J Du M ., J. Chin. Chem Lett, 2007, 18( 65-68
[8]	Zou K., Wu J Liu C ., J. Chin. Chem Lett, 2006, 17( 1355-1338
[9]	Zou K., Jun W Ming D ., J. Chin. Chem Lett, 2006, 18( 65-68
[10]	Zou K., Wang J. Z., Du M ., J. Chem. Pharm Bull, 2006, 54( 1440-1442
[11]	Wu H. Y., Wang Q., Liu C. X., Zou K., ., Journal of China Three Gorges University(Natural Science), 2012, 34, 85-88
	( 邬昊洋, 王倩, 刘呈雄, 邹坤 . 三峡大学学报自然科学版, 2012, 34, 85-88)
[12]	Wu G. X., Liu A. Y., Wei X. Y., Chen W. X ., Journal of Wuhan Botanical Research, 2007, 25, 89-92
	( 吴光旭, 刘爱媛, 魏孝义, 陈维信 . 武汉植物学研究, 2007, 25, 89-92)
[13]	Pan W. B., Wei L. M., Wei L. L., Wu Y. C ., Chem. Pharm Bull, 2006, 54( 954-958
[14]	Pan W. B., Chang F. R., Wei L. M., Wu Y. C ., J. Nat Prod, 2003, 66( 161-168
[15]	Pan W. B., Chang F. R ., J. Chem. Pham Bull, 2000, 48( 9), 1350-1353
[16]	Pan W. B., Chang F. R., Wu Y. C ., J. Nat. Prod 2000, 63( 861-863
[17]	Li Q., Zou K., Wang J. Z., ., Chinese Journal of Ethnomedicine and Ethnopharmacy, 2007, 86, 164-167
	( 李青, 邹坤, 汪鋆植 . 中国民族民间医药杂志, 2007, 86, 164-167)
[18]	Cai J., Zhu Z. G., Xu C. L ., Journal of Southern Medical University, 2007, 27, 188-194
	( 蔡晶, 朱正光, 余传林 . 南方医科大学学报, 2007, 27, 188-194)
[19]	Xiao Y. H., Yin H. L Chen L. Dong J. X., ., Fitoterapia, 2015, 102( 102-108
[20]	Situ Z Q.. Wu J. Z ., Cell Culture(Revised Edition), World Publishing Corporation, Xi'an, 2004
	( 司徒镇强, 吴军正 . 细胞培养修订版, 西安: 世界图书出版公司, 2004)
[21]	Miyahara K., Kudo K., Kawasaki T ., Chem. Pharm Bull, 1983, 31( 348-351
[22]	Tobari A., Teshima M., Koyanagi J., Kawase M ., Eur. J. Med Chem, 2000, 35( 511-527
[23]	Inoue T., Mimaki Y., Sashida Y., Nikaido T., Ohmoto T ., Phytochemistry, 1995, 39( 1103-1110
[24]	Patricia Y. H., Aisyah H. J., Reg L., Kerry P., William K., James J. D ., Phytochemistry, 2008, 69( 796-804
[25]	Pawan K. A ., Phytochemistry, 1992, 31( 3307-3313
[26]	Pan Z. H., Li Y., Liu J. L., Ning D. S., Li D. P., Wu X. D., Wen Y. X ., Fitoterapia, 2012, 83( 1489-1493
[27]	Shen P., Wang S. L., Yang C. R., Cai B., Yao X. S ., Acta Bota. Sinica 2003, 45( 5), 626-629
[28]	Wang Q., Miao W. J., Xiang C., Guo D. A., Ye M., ., Chinese Traditional and Herbal Drugs 2014, 45, 31-35
	( 王青, 苗文娟, 向诚, 果德安, 叶敏 . 中草药, 2014, 45, 31-35)
[29]	Elsohly H. N., Joshi A., Li X. C., Ross S. A ., Phytochemistry, 1999, 52( 141-145
[30]	Qi L. K., Wang J., Liu H. Z ., Chinese Journal of Biochemical Pharmaceutics, 2015, 2, 45-47
	( 戚利坤, 王俊, 刘洪泽 . 中国生化药物杂志, 2015, 2, 45-47)

C atom	δ_H(J/Hz)	Key NOESY	δ_C	Key HMBC
1	4.55(d, 6.4)	3-H	72.2(CH)	C3
2	2.39(m), 2.01(m)		33.0(CH₂)
3	2.01(m)	1-H	74.4(CH)
4	4.41(d, 5.2), 2.31(m)		30.8(CH₂)
5	1.97(m)		35.3(CH)	C3
6	2.02(m)		26.3(CH₂)
7	1.70(m), 1.56(m)		26.4(CH₂)
8	1.66(m), 1.30(m)		31.8(CH)
9	1.87(m)		42.0(CH)
10	1.16(m)		41.0(C)
11			20.9(CH₂)
12	2.00(m), 1.42(m)		40.4(CH₂)
13	1.63(m), 1.04(m)		40.2(C)
14		16-H, 17-H	55.3(CH)
15	1.06(m)		30.5(CH₂)
16	1.84(m), 1.45(m)	14-H, 23-H	80.6(CH)
17	4.36(d, 7.2), 1.54(m)	14-H	62.5(CH)
18	0.94(s)	20-H	19.0(CH₃)	C14, C17
19	1.22(s)		16.5(CH₃)	C1, C5, C6, C9
20	2.29(m)	18-H	42.0(CH)
21	1.00(d, 6.4)		16.8(CH₃)	C20, C22
22			110.4(C)
23	1.69(m), 1.49(m)	16-H	28.1(CH₂)
24	1.51(m), 1.34(m)		28.0(CH₂)
25	1.65(m)		29.0(CH)
26	3.69(d, 7.2), 3.63(d, 7.2)		69.5(CH₂)
27	0.66(d, 6.4)		17.2(CH₃)	C24, C25, C26
1'	5.01(d, 8.0)		101.1(CH)	C3
2'	3.98(dd, 8.0, 4.0)		74.9(CH)
3'	3.95(dd, 8.0, 4.0)		78.5(CH)
4'	4.26(dd, 8.4, 4.4)		71.4(CH)
5'	4.24(dd, 8.4, 4.4)		78.5(CH)
6'	4.57(dd, 9.2, 3.6), 4.36(dd, 9.2, 3.6)		62.5(CH₂)

C atom	δ_H(J/Hz)	Key NOESY	δ_C	Key HMBC
1	4.55(d, 6.4)	3-H	72.2(CH)	C3
2	2.39(m), 2.01(m)		33.0(CH₂)
3	2.01(m)	1-H	74.4(CH)
4	4.41(d, 5.2), 2.31(m)		30.8(CH₂)
5	1.97(m)		35.3(CH)	C3
6	2.02(m)		26.3(CH₂)
7	1.70(m), 1.56(m)		26.4(CH₂)
8	1.66(m), 1.30(m)		31.8(CH)
9	1.87(m)		42.0(CH)
10	1.16(m)		41.0(C)
11			20.9(CH₂)
12	2.00(m), 1.42(m)		40.4(CH₂)
13	1.63(m), 1.04(m)		40.2(C)
14		16-H, 17-H	55.3(CH)
15	1.06(m)		30.5(CH₂)
16	1.84(m), 1.45(m)	14-H, 23-H	80.6(CH)
17	4.36(d, 7.2), 1.54(m)	14-H	62.5(CH)
18	0.94(s)	20-H	19.0(CH₃)	C14, C17
19	1.22(s)		16.5(CH₃)	C1, C5, C6, C9
20	2.29(m)	18-H	42.0(CH)
21	1.00(d, 6.4)		16.8(CH₃)	C20, C22
22			110.4(C)
23	1.69(m), 1.49(m)	16-H	28.1(CH₂)
24	1.51(m), 1.34(m)		28.0(CH₂)
25	1.65(m)		29.0(CH)
26	3.69(d, 7.2), 3.63(d, 7.2)		69.5(CH₂)
27	0.66(d, 6.4)		17.2(CH₃)	C24, C25, C26
1'	5.01(d, 8.0)		101.1(CH)	C3
2'	3.98(dd, 8.0, 4.0)		74.9(CH)
3'	3.95(dd, 8.0, 4.0)		78.5(CH)
4'	4.26(dd, 8.4, 4.4)		71.4(CH)
5'	4.24(dd, 8.4, 4.4)		78.5(CH)
6'	4.57(dd, 9.2, 3.6), 4.36(dd, 9.2, 3.6)		62.5(CH₂)

Compd.	IC₅₀/(μmol·L^-1)		Compd.	IC₅₀/(μmol·L^-1)
Compd.	LoVo	BGC-823	Compd.	LoVo	BGC-823
1	>6.0	>5.0	5/6	0.532±0.139^*	0.757±0.093^*
2	>6.0	>5.0	7	4.731±0.157	3.679±0.083
3	3.232±0.141	4.833±0.097	8	>6.0	5.538±0.207
4	>6.0	>5.0	Cisplatin	5.725±0.272	4.623±0.742

Compd.	IC₅₀/(μmol·L^-1)		Compd.	IC₅₀/(μmol·L^-1)
Compd.	LoVo	BGC-823	Compd.	LoVo	BGC-823
1	>6.0	>5.0	5/6	0.532±0.139^*	0.757±0.093^*
2	>6.0	>5.0	7	4.731±0.157	3.679±0.083
3	3.232±0.141	4.833±0.097	8	>6.0	5.538±0.207
4	>6.0	>5.0	Cisplatin	5.725±0.272	4.623±0.742