Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

doi:10.6023/cjoc202003062

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

去氢枞酸硝酸酯类化合物的合成及细胞毒性评价

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

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 E-mail:wgduan@gxu.edu.cn
基金资助:
广西自然科学基金（Nos.2018GXNSFAA138165，2018GXNSFAA281200）、省部共建药用资源化学与药物分子工程国家重点实验室资助课题（广西师范大学）（No.CMEMR2019-B02）、广西林产化学与工程重点实验室开放基金课题（No.GXFC18-02）、广西农产资源化学与生物技术重点实验室开放基金（No.2019KF06）、广西高等学校千名中青年骨干教师培育计划、广西高校中青年科研基础能力提升项目（No.2019KY051）和桂林医学院中青年教职工科研基础能力提升（No.2018glmcy015）资助项目.

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

Li Fangyao^a,b, Huang Lin^b, Zhou Xiaoqun^b, Li Qian^b, Ma Xianli^b, Duan Wengui^a, Wang Xiu^a

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).

1. cjoc202003062辅助材料.pdf(2500KB)

Abstract

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

Cite this article

Li Fangyao, Huang Lin, Zhou Xiaoqun, Li Qian, Ma Xianli, Duan Wengui, Wang Xiu. Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety[J]. Chinese Journal of Organic Chemistry, 2020, 40(9): 2845-2854.

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去氢枞酸硝酸酯类化合物的合成及细胞毒性评价

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

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