18β-甘草次酸A环开环衍生物的合成及抗肿瘤活性

高等学校化学学报 ›› 2010, Vol. 31 ›› Issue (9): 1762.

18β-甘草次酸A环开环衍生物的合成及抗肿瘤活性

胡君¹, 吴洋¹, 赵长崎², 巨勇^1,3

1. 清华大学化学系, 生命有机磷化学及化学生物学教育部重点实验室, 北京100084;
2. 北京师范大学生命科学学院, 北京100875;
3. 兰州大学功能有机分子化学国家重点实验室, 兰州730000

收稿日期:2009-12-15 出版日期:2010-09-10 发布日期:2010-09-10
通讯作者: 巨勇, 男, 博士, 教授, 博士生导师, 主要从事有机化学及化学生物学研究. E-mail: juyong@mail.tsinghua.edu.cn
基金资助:
国家自然科学基金(批准号: 20772071, 20972086) 和高等学校博士学科点基金(批准号: 20090002110060)资助.

Synthesis and Anti-tumor Activity of Opened A-Ring Modified 18β-Glycyrrhetinic Acid Derivatives

HU Jun¹, WU Yang¹, ZHAO Chang-Qi², JU Yong^1,3*

1. Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China;
2. School of Life Science, Beijing Normal University, Beijing 100875, China;
3. State Key Laboratory of Applied Organic Chemistry Lanzhou University, Lanzhou 730000, China

Received:2009-12-15 Online:2010-09-10 Published:2010-09-10
Contact: JU Yong. E-mail: juyong@mail.tsinghua.edu.cn
Supported by:
国家自然科学基金(批准号: 20772071, 20972086) 和高等学校博士学科点基金(批准号: 20090002110060)资助.

摘要/Abstract

摘要： 采用化学方法在18β-甘草次酸A环上进行结构修饰, 合成了一系列新颖的A环具有不同官能团的开环衍生物. 初步研究了它们对人体肝癌细胞HepG-2的体外细胞毒活性, 结果表明, 羟基的数目和位置对抑制HepG-2细胞增殖起着重要的作用.

关键词: 18β-甘草次酸, 三萜, 抗肿瘤活性

Abstract: Glycyrrhetinic acid, a facile pentacyclic triterpenoid with rigid and chiral structures, is widely present in the form of aglycone or glycosides in medicinal plants, which is used as bioactive component on anti-inflammatory, anti-viral and anti-tumor-promotion effect. Owing to its relative low-toxicity, biocompatibility and bioactivity, a series of novel opened A-ring and different functional group derivatives of glycyrrhetinic acid was synthesized by chemical methods. The preliminary biological activities were tested against human liver carcinoma(HepG-2) cell in vitro. The results show that the activity should be affected by the number and the position of hydroxyls.

Key words: 18β-Glycyrrhetinic acid, Triterpenoids, Anti-tumor activity

TrendMD:

胡君, 吴洋, 赵长崎, 巨勇. 18β-甘草次酸A环开环衍生物的合成及抗肿瘤活性. 高等学校化学学报, 2010, 31(9): 1762.

HU Jun, WU Yang, ZHAO Chang-Qi, JU Yong*. Synthesis and Anti-tumor Activity of Opened A-Ring Modified 18β-Glycyrrhetinic Acid Derivatives. Chem. J. Chinese Universities, 2010, 31(9): 1762.

参考文献

[1]Shi J. H., Zhou Y. X., He M. L., Jin J., Xiao Y. C., Xiao J. H., Wei D. Z.. Chem. Nat. Comp.[J], 2006, 42: 325—327 [2]Um S. J., Park M. S., Park S. H., Han H. S., Kwon Y. J., Sin H. S.. Bioorg. Med. Chem.[J], 2003, 11: 5345—5352 [3]Yoshida K., Furihata K., Habe H., Yamane H., Omori T.. Biotechnol. Lett.[J], 2001, 23: 1619—1624 [4]Morana A., Di Lazzaro A., Di Lernia I., Ponzone C., De Rosa M.. Biotechnol. Lett.[J], 2002, 24: 1907—1911 [5]Fusako T., Toru E., Yasumitsu Y.. Jpn. Pharmacol. Ther.[J], 2000, 28: 763—770 [6]Fore C., Eisenhut M., Ragazzi E., Zanchin G., Armanini D.. J. Ethnopharmacol.[J], 2005, 99: 317—324 [7]Yang J., Zhou L., Wang J. P., Wang G. J., Davey A.. Planta Med.[J], 2008, 74: 1351—1356 [8]Shimoyama Y., Hirabayashi K., Matsumoto H., Sato T., Shibata S., Inoue H.. J. Pharm. Pharmacol.[J], 2003, 55: 811—817 [9]Yu D. L., Sakurai Y., Chen C. H., Chang F. R., Huang L., Kashiwada Y., Lee K. H.. J. Med. Chem.[J], 2006, 49: 5462—5469 [10]Kim H. K., Park Y., Kim H. N., Choi B. H., Jeong H. G., Lee D. G., Hahm K. S.. Biotechnol. Lett.[J], 2002, 24: 1899—1902 [11]Hiroaki T., Hiraku O., Yoshiharu M.. J. Pharm. Pharmacol.[J], 2004, 56: 437—444 [12]Park H. Y., Park S. H., Yoon H. K., Han M. J., Kim D. H.. Arch. Pharm. Res.[J], 2004, 27: 57—60 [13]Shin Y. W., Bae E. A., Lee B., Lee S. H., Kim J. A., Kim Y. S., Kim D. H.. Planta Med.[J], 2007, 73: 257—261 [14]Chadalapaka G., Jutootu I., McAlees A., Stefanac T., Safe S.. Bioorg. Med. Chem. Lett.[J], 2008, 18: 2633—2639 [15]Chintharlapalli S., Papineni S., Jutooru I., McAlees A., Safe S.. Mol. Cancer Ther.[J], 2007, 6: 1588—1598 [16]Tatsuzaki J., Taniguchi M., Bastow K. F., Nakagawa-Goto K., Morris-Natschke S. L., Itokawa H., Baba K., Lee K. H.. Bioorg. Med. Chem.[J], 2007, 15: 6193—6199 [17]Lee C. S., Kim Y. J., Lee M. S., Han E. S., Lee S. J.. Life Sci.[J], 2008, 83: 481—489 [18]Su X. D., Lawrence H., Ganeshapillai D., Cruttenden A., Purohit A., Reed M. J., Vicker N., Potter B. V. L.. Bioorg. Med. Chem.[J], 2004, 12: 4439—4457 [19]Zhai D. S., Zhao Y., Chen X. J., Guo J. Q., He H., Yu Q. L., Yang J. N., Davey A. K., Wang J. P.. Planta Med.[J], 2007, 73: 128—133 [20]Liu D., Song D. D., Guo G., Wang R., Lv J. L., Jing Y. K., Zhao L. X.. Bioorg. Med. Chem.[J], 2007, 15: 5432—5439 [21]Askam V., Baines C. M., Smith H. J.. J. Pharm. Pharmacol.[J], 1966, 18: 168—174 [22]Terasawa T., Okada T., Hara T., Itoh K.. Eur. J. Med. Chem.[J], 1992, 27: 345—351 [23]Anja N., Alexander B., Ralph K., Alexander K., Dieter S., Stefan S., Rene C.. Arch. Pharm.[J], 2009, 342: 569—576 [24]XIONG Yi(熊轶), WANG Kui-Wu(王奎武), PANG Yuan-Jiang(潘远江), SUN Hong-Xiang(孙红祥). Chem. J. Chinese Universities(高等学校化学学报)[J], 2006, 27(11): 2101—2105 [25]Wahhab A., Ottosen M., Bachelor F. W.. Can. J. Chem.[J], 1991, 69: 570—577 [26]Klinotova E., Krecek Vaclav., Klinot J., Endova M., Eisenreichova J., Budesinsky M., Sticha M.. Collect. Czech. Chem. Commun.[J], 1997, 62, 1776—1798 [27]Gnoatto S. C. B., Dassonville-Klimpt A., Da Nascimento S., Galera P., Boumediene K., Gosmann G., Sonnet P., Moslemi S.. Eur. J. Med. Chem.[J], 2008, 43: 1865—1877