18β-甘草次酸吡啶酰胺衍生物体外抗肿瘤活性研究

doi:10.16431/j.cnki.1671-7236.2015.11.002

›› 2015, Vol. 42 ›› Issue (11): 2822-2832.doi: 10.16431/j.cnki.1671-7236.2015.11.002

18β-甘草次酸吡啶酰胺衍生物体外抗肿瘤活性研究

吴越¹, 张玉彦², 李学强³, 周学章¹

1. 西部特色生物资源保护与利用教育部重点实验室, 银川 750021;
2. 宁夏智弘生物科技有限公司, 银川 750021;
3. 宁夏大学化学化工学院, 银川 750021

收稿日期:2015-02-02 出版日期:2015-11-20 发布日期:2015-11-26
通讯作者: 周学章 E-mail:zhouxuezhang@nxu.edu.cn
作者简介:吴越(1989-),女,宁夏银川人,硕士生,研究方向:微生物与基因工程,E-mail:nomoon_sky@hotmail.com
基金资助:
国家自然科学基金(31260624、31460676)

Study on Anti-tumor Activity of 18β-glycyrrhetinic Acid Derivatives Containing Pyridine Carboxamide in vitro

WU Yue¹, ZHANG Yu-yan², LI Xue-qiang³, ZHOU Xue-zhang¹

1. Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in Western China, Yinchuan 750021, China;
2. Zoohance Biotechnology Co., Ltd., Yinchuan 750021, China;
3. College of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021, China

Received:2015-02-02 Online:2015-11-20 Published:2015-11-26

摘要/Abstract

摘要： 本试验研究18β-甘草次酸吡啶酰胺衍生物6c、10c、11c对HeLa、SMMC-7721、SGC-7901细胞增殖的影响。利用MTT法检测18β-甘草次酸吡啶酰胺衍生物6c、10c、11c对HeLa、SMMC-7721、SGC-7901细胞的抑制率;利用Hoechst-33258细胞凋亡染色试剂盒检测细胞凋亡情况;用Annexin V-FITC/PI双染法检测细胞凋亡率;蛋白质免疫印迹法检测相关蛋白表达水平;通过检测Caspases-3的活性进一步说明用药组诱导细胞凋亡的情况。结果表明,18β-甘草次酸吡啶酰胺衍生物6c、10c、11c对HeLa、SMMC-7721、SGC-7901细胞增殖均有抑制作用及促凋亡作用,且呈浓度依赖性,经t检验均有统计学意义(P<0.05)。18β-甘草次酸吡啶酰胺衍生物6c、10c、11c可诱导HeLa、SMMC-7721、SGC-7901细胞凋亡。

关键词: 18β-甘草次酸吡啶酰胺衍生物; HeLa细胞; SMMC-7721细胞; SGC-7901细胞

Abstract: The assay was aimed to study the effect of 18β-glycyrrhetinic acid derivatives containing pyridine carboxamide 6c,10c and 11c on the proliferation of HeLa,SMMC-7721 and SGC-7901 cells.Detected the cellular inhibition rate of 18β-glycyrrhetinic acid derivatives containing pyridine carboxamide 6c,10c and 11c to HeLa,SMMC-7721 and SGC-7901 cells by MTT method;Detected the conditions of apoptosis by Hoechst-33258 Staining Kit;Detected the apoptosis rate by Annexin V-FITC/PI method;The related protein expression levels were detected by Western blotting;To further clarify the situation of apoptosis induced in treatment group by detecting the activity of Caspases-3.18β-glycyrrhetinic acid derivatives containing pyridine carboxamide 6c,10c and 11c had the inhibition and promoting apoptosis effects on the proliferation of HeLa,SMMC-7721 and SGC-7901 cells,and had the concentration dependence.The results all showed statistical significance in t test (P<0.05).18β-glycyrrhetinic acid derivatives containing pyridine carboxamide 6c,10c and 11c could induce the apoptosis of HeLa,SMMC-7721 and SGC-7901 cells.

Key words: 18β-glycyrrhetinic acid derivatives containing pyridine carboxamide; HeLa cell; SMMC-7721 cell; SGC-7901 cell

中图分类号:

R966

吴越, 张玉彦, 李学强, 周学章. 18β-甘草次酸吡啶酰胺衍生物体外抗肿瘤活性研究[J]. , 2015, 42(11): 2822-2832.

WU Yue, ZHANG Yu-yan, LI Xue-qiang, ZHOU Xue-zhang. Study on Anti-tumor Activity of 18β-glycyrrhetinic Acid Derivatives Containing Pyridine Carboxamide in vitro[J]. , 2015, 42(11): 2822-2832.

参考文献

[1] 颜苗,李兰芳,李焕德,等.甘草次酸18位差向异构体对Caco-2细胞P-糖蛋白功能和表达的影响[J].中国药学杂志,2012,49(1):8-12.
[2] Malagoli M,Castelli M,Baggio A,et al.Effect of glycyrrhizin and its diastereoisomers on the growth of human tumor cells:Preliminary finding[J].Phytother Res,1998,12(2):95-97.
[3] 高振北,胡君,康潇,等.18β-甘草次酸A环官能团化衍生物的合成及抗肿瘤活性[J].高等化学学报,2012,33(4):750-754.
[4] Shetty A V,Thirugnanam S,Dakshinamoorthy G,et al.18α-glycyrrhetinic acid targets prostate cancer cells by down regulating inflammation related genes[J].Int J Oncol,2011,39(3):635-640.
[5] Hu L N,Fang X Y,Liu H L,et al.Protective effects of 18β-glycyrrhetinic acid on LPS-induced injury in intestinal epithelial cells[J].Chinese Journal of Natural Medicines,2013,11(1):24-29.
[6] 黄炜,陈新美,张志凌,等.18β-甘草次酸诱导人乳腺癌细胞凋亡及其细胞内Ca²⁺水平的变化[J].中国癌症杂志,2006,6(2):102-106.
[7] Chen C X,Li X Q,Li T C,et al.Synthesis and anti-tumor activities of novel 18β-glycyrrhetinic acid derivatives attaching dithiocarbamate units[J].Acta Chimica Sinica,2012,70(7):852-858.
[8] 邢立群,贾芳.甘草次酸联合抗结核药对结核杆菌活性研究[J].中国畜牧兽医,2014,41(4):160-164.
[9] Sirisoma N,Pervin A,Zhang H,et al.Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine,a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier pentration[J].J Med Chem,2009,52(8):2341-2351.
[10] Gottfried S,Lily B.Glycyrrheinic acid derivatives[P].GB:843133,1960-08-04.
[11] Takiura K,Honda S,Yamamoto M,et al.Studies of oligosaccharides.Ⅻ.Hydrophilization of glycyrrhetinic acid by coupling to gentio oligosaccharides[J].Chemical and PharmaceuticalBulletin,1974,22(7):1618-1623.
[12] Farag M A,Porzel A,Wessjohann L A.Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species[J].Journal of Advanced Research,2015,6(1):99-104.
[13] Krausse R,Bielenberg J,Blaschek W,et al.In vitro anti-helicobacter pylori activity of extractum liquirtiae glycyrrhizin and its metabolites[J].The Journal of Antimicrobial Chemotherapy,2004,54(1):243-246.
[14] 罗惠玲,黄炜,张志凌,等.18β-甘草次酸诱导人乳腺癌细胞凋亡及与细胞内Ca²⁺释放的关系(英文)[J].The Chinese-German Journal of Clinical Oncology,2004,3:162-164.
[15] 金敏,吴红金.甘草次酸药理作用的研究进展[J].医学综述,2009,15(11):1712-1715.
[16] Hoever G,Baltina L,Michaelis M.Antiviral activity of glycyrrhizic acid derivatives against SARS coronavirus[J].J Med Chem,2005,48:1256.
[17] 孟艳秋,杨哲,张萌,等.甘草次酸C3、C11、C30衍生物的合成及其体外抗肿瘤活性研究[J].现代药物与临床,2014,29(1):6-10.
[18] Su X D,Vicker N,Potter B V L,et al.Inhibition of human and rat 11β-hydroxysteroid dehydrogenase type 1 by 18β-glycyrrhetinic acid derivatives[J].J Steroid Biochem Molecu Biology,2007,104(3-5):312-320.
[19] Lee K H,Tatsuzaki J,Taniguchi M,et al.Anti-tumor agents 255:Novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents[J].Bioorg Med Chem,2007,15:6193-6199.
[20] Hu J,Zhang M,Ju Y,et al.Synthesis and binding ability of 1,2,3-triazole-based triterpenoid receptors for recognition of Hg²⁺ ion[J] .Bioorg Med Chem Lett,2010,20:4342-4345.
[21] 巨勇,高振北,胡君,等.18β-甘草次酸A环官能团化衍生物的合成及抗肿瘤活性[J].高等学校化学学报,2012,33(4):750-754.
[22] 刘丹,寇丽影,崔婷秀,等.18β-甘草次酸类衍生物的合成及抑制白血病细胞生长和诱导细胞凋亡活性研究[J].中国药物化学杂志,2010,20(94):84-89.
[23] Liu D,Song D D,Guo G.The synthesis of 18β-glycyrrhetinic acid derivatives which have increased antiproliferative and apoptotic effects in leukemia cells[J].Bioorg Med Chem,2007,15:5432-5439.
[24] Moon M H,Jeong J K,Lee Y J,et al.18β-glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis[J].Biochemical and Biophysical Research Communications,2012,420(4):805-810.
[25] Huang L,Yu D L,Phong H,et al.Synthesis and proteasome inhibition of glycyrrhetinic acid derivatives[J].Bioorg Med Chem,2008,16:6696-6699.
[26] 雍建平.甘草酸、甘草次酸衍生物的合成及生物活性研究进展[J].时珍国医国药,2012,23(6):1495-1498.

18β-甘草次酸吡啶酰胺衍生物体外抗肿瘤活性研究

Study on Anti-tumor Activity of 18β-glycyrrhetinic Acid Derivatives Containing Pyridine Carboxamide in vitro

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