Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (9): 2845-2854.DOI: 10.6023/cjoc202003062 Previous Articles     Next Articles


李芳耀a,b, 黄琳b, 周小群b, 李倩b, 马献力b, 段文贵a, 王秀a   

  1. a 广西大学化学化工学院 南宁 530004;
    b 桂林医学院药学院 广西桂林 541004
  • 收稿日期:2020-03-29 修回日期:2020-05-23 发布日期:2020-06-28
  • 通讯作者: 段文贵
  • 基金资助:

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

Li Fangyaoa,b, Huang Linb, Zhou Xiaoqunb, Li Qianb, Ma Xianlib, Duan Wenguia, Wang Xiua   

  1. a School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004;
    b School of Pharmacy, Guilin Medical University, Guilin, Guangxi 541004
  • Received:2020-03-29 Revised:2020-05-23 Published:2020-06-28
  • Supported by:
    Project supported by the Guangxi Natural Science Foundation of China (Nos. 2018GXNSFAA138165, 2018GXNSFAA281200), the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) (No. CMEMR2019-B02), the Open Fund of Guangxi Key Laboratory of Chemistry and Engineering of Forest Products (No. GXFC18-02), the Open Fund of Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology (No. 2019KF06), the Cultivating Project of a Thousand of Young and Middle-Aged Key Teachers in Guangxi Colleges and Universities, the Youth Promotion Project Fund of Guangxi (No. 2019KY0551), and the Project to Improve the Basic Research Ability of Middle and Young Teachers in Guilin Medical University (No. 2018glmcy015).

In order to find more effective antitumor agents, a series of novel dehydroabietic acid derivatives bearing nitrate moiety were designed and synthesized. Their cytotoxicities were evaluated against human cancer cell lines of CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical) and BEL-7402 (liver), and human normal liver cell (HL-7702) and nasopharyngeal epithelial cell (NP69) using methyl thiazolyl tetrazolium (MTT) assay. Biological screening results demonstrated that most of the hybrids exhibited more potent cytotoxicity superior to parent compound dehydroabietic acid. Among them, 12-bromodehydroabietic acid-3'-nitrooxypropyl ester (5j) displayed better antiproliferative activity with IC50value of (8.36±0.14) μmol/L toward CNE-2 cells compared with cisplatin, and 2,14-dinitrodehydroabietic acid-3'-nitrooxypropyl ester (5n) showed remarkable cytotoxicity with IC50 value of (11.23±0.21) μmol/L against BEL-7402 cells. Moreover, they exhibited lower cytotoxicity against human normal liver cell line HL-7702 and nasopharyngeal epithelial cell NP69. Besides, NO released amounts detection of all nitrates suggested that in most cases, the cytotoxicities were positively correlated with the levels of intracellular NO release in CNE-2 cells.

Key words: dehydroabietic acid, nitrate, synthesis, cytotoxicity