广西师范大学学报（自然科学版） ›› 2021, Vol. 39 ›› Issue (2): 132-138.doi: 10.16088/j.issn.1001-6600.2020011603

• CCIR2020 • 上一篇    下一篇

齐墩果酸-对羟基苯甲腈及其类似物的合成与抗肿瘤活性评价

刘晶晶1,2, 陈转欣1,2, 尤佳航1,2, 黄家艳1,2, 程克光1,2*   

  1. 1.省部共建药用资源化学与药物分子工程国家重点实验室广西师范大学, 广西 桂林541004;
    2.广西师范大学 化学与药学学院, 广西 桂林541004
  • 收稿日期:2020-01-16 修回日期:2020-03-03 出版日期:2021-03-25 发布日期:2021-04-15
  • 通讯作者: 程克光(1983—),女,湖北荆州人,广西师范大学教授,博士。E-mail:kgcheng2008@gmail.com
  • 基金资助:
    国家自然科学基金(21562006);广西自然科学基金(2015GXNSFAA139186);广西医药产业人才小高地项目(1506);药用资源化学与药物分子工程教育部重点实验室资助课题(CMEMR2013-A01,CMEMR2013-C02)

Synthesis and Antitumor Activity Evaluation of Oleanolic Acid-p-hydroxybenzonitrile and Its Analogues

LIU Jingjing1,2, CHEN Zhuanxin1,2, YOU Jiahang1,2, HUANG Jiayan1,2, CHENG Keguang1,2*   

  1. 1. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources Guangxi Normal University, Guilin Guangxi 541004, China;
    2. School of Chemistry and Pharmacy, Guangxi Normal University, Guilin Guangxi 541004, China
  • Received:2020-01-16 Revised:2020-03-03 Online:2021-03-25 Published:2021-04-15

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摘要： 以齐墩果酸、熊果酸和甘草次酸为原料,在碱性条件下,与二溴烷烃反应生成溴代烷烃酯;继而与对羟基苯甲腈发生亲核取代反应,共合成得到6个齐墩果酸/熊果酸/甘草次酸-对羟基苯甲腈缀合物,并采用MTT法测试其抗肿瘤活性。结果显示:[(4-氰基苯氧基)-正己基]-甘草次酸酯和[(4-氰基苯氧基)-正辛基]-甘草次酸酯对慢性髓系白血病细胞系K562有一定的抗增殖作用,其中[(4-氰基苯氧基)-正己基]-甘草次酸酯对人肝肿瘤细胞系Bel-7402也有中等抗增殖作用,其余化合物对所测细胞都没有抗增殖活性。[(4-氰基苯氧基)-正己基]-甘草次酸酯对测试细胞的抗增殖活性与阳性对照药5-FU相当,对正常肝细胞损伤较少,具有进一步研究的潜在价值。

关键词: 齐墩果酸, 熊果酸, 甘草次酸, 对羟基苯甲腈, 抗肿瘤活性

Abstract: Oleanolic acid, ursolic acid and glycyrrhetinic acid were esterified with corresponding α,ω-dibromoalkane in the presence of potassium carbonate to prepare intermediates. Then, the intermediates were treated with p-hydroxybenzonitrile under potassium carbonate by means of a nucleophilic substitution reaction to generate six oleanolic acid/ursolic acid/glycyrrhetinic acid-p-hydroxybenzonitrile derivatives. Anti-tumor activity was tested by the MTT assay. The results showed that glycyrrhetinic acid-p-hydroxybenzonitrile conjugates [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate and [n-(4-cyanophenoxy)-octyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate had certain anti-proliferative effect on chronic myeloid leukemia cell line K562. Moreover, [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate also had moderate anti-proliferative effect on human liver tumor cell line Bel-7402. Other compounds had no antiproliferative activity on the tested cell lines. [n-(4-Cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oate, which has less damage to normal liver cells, expressed almost the same level as the positive control drug 5-FU on the anti-proliferative activity of the tested cells. This indicated that [n-(4-cyanophenoxy)-hexyl]-3β-hydroxy-11-oxo-olean-12-en-29-oateand had the potential value for further research in anti-tumor field.

Key words: oleanolic acid, ursolic acid, glycyrrhetinic acid, p-hydroxybenzonitrile, antitumor activity

中图分类号: 

  • R914
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