Citation: 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. doi: 10.6023/cjoc202003062 shu

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

Corresponding author: Duan Wengui, wgduan@gxu.edu.cn
Received Date: 29 March 2020
Revised Date: 23 May 2020
Available Online: 24 June 2020
Fund Project: the Open Fund of Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology 2019KF06the Guangxi Natural Science Foundation of China 2018GXNSFAA281200the Project to Improve the Basic Research Ability of Middle and Young Teachers in Guilin Medical University 2018glmcy015the Open Fund of Guangxi Key Laboratory of Chemistry and Engineering of Forest Products GXFC18-02Project 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)the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) CMEMR2019-B02the Guangxi Natural Science Foundation of China 2018GXNSFAA138165the Youth Promotion Project Fund of Guangxi 2019KY051

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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.
- dehydroabietic acid,
- nitrate,
- synthesis,
- cytotoxicity
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