SIOC 中文
CJOG
Adv search

Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 9: 2845 - 2854

DOI: https://doi.org/10.6023/cjoc202003062

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Nitrate Moiety

  • Li Fangyao ,
  • Huang Lin ,
  • Zhou Xiaoqun ,
  • Li Qian ,
  • Ma Xianli ,
  • Duan Wengui ,
  • Wang Xiu
Expand
  • a School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004;
    b School of Pharmacy, Guilin Medical University, Guilin, Guangxi 541004

Received date: 2020-03-29

  Revised date: 2020-05-23

  Online 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).

Fold

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 . DOI: 10.6023/cjoc202003062

References

[1] Li, Z.-S.; Li, J.-F.; Liu, H.; Shang, S.-B.; Song, Z.-Q. Chem. Ind. Forest. Prod. 2018, 38, 17(in Chinese). (李兆双, 李建芳, 刘鹤, 商士斌, 宋湛谦, 林产化学与工业, 2018, 38, 17.)
[2] Rao, X.; Song, Z.; He, L.; Jia, W. Chem. Pharm. Bull. 2008, 56, 1575.
[3] Huang, X. C.; Jin, L.; Wang, M.; Liang, D.; Chen, Z. F.; Zhang, Y.; Pan, Y. M.; Wang, H. S. Eur. J. Med. Chem. 2015, 89, 370.
[4] Hou, W.; Luo, Z.; Zhang, G.; Cao, D.; Li, D.; Ruan, H.; Ruan, B. H.; Su, L.; Xu, H. Eur. J. Med. Chem. 2017, 138, 1042.
[5] Gu, W.; Miao, T. T.; Hua, D. W.; Jin, X. Y.; Tao, X. B.; Huang, C. B.; Wang, S. F. Bioorg. Med. Chem. Lett. 2017, 27, 1296.
[6] Huang, X.; Huang, R.; Liao. Z.; Pan, Y.; Gou, S.; Wang, H. Eur. J. Med. Chem. 2016, 108, 381.
[7] Huang, X. C.; Wang, M.; Pan, Y. M.; Yao, G. Y.; Wang, H. S.; Tian, X. Y.; Qin, J. K.; Zhang, Y. Eur. J. Med. Chem. 2013, 69, 508.
[8] Zhang, W. M.; Yao, Y.; Yang, T.; Wang, X. Y.; Zhu, Z. Y.; Xu, W. T.; Lin, H. X.; Gao, Z. B.; Zhou, H.; Yang, C. G.; Cui, Y. M. Bioorg. Med. Chem. Lett. 2018, 28, 1943.
[9] da Silva, K. R.; Damasceno, J. L.; Inácio, M. O.; Abrão, F.; Ferreira, N. H.; Tavares, D. C.; Ambrosio, S. R. Front Microbiol. 2018, 65, 538.
[10] Zhou, Z.; Zhou, T. J. Chem. Res. 2018, 42, 405.
[11] Pertino, M. W.; Vega, C.; Rolón, M.; Coronel, C.; Arias, A.R.; Hirschmann, G. S. Molecules 2017, 22, 369.
[12] Fonseca, T.; Gigante, B.; Marques, M. M.; Gilchrist, T. L.; De Clercq, E. Bioorg. Med. Chem. 2004, 12, 103.
[13] Savluchinske-Feio, S.; Nunes, L.; Pereira, P. T.; Silva, A. M.; Roseiro, J. C.; Gigante, B.; Marcelo Curto, M. J. J. Microbiol. Methods 2007, 70, 465.
[14] Chen, N.; Duan, W.; Lin, G.; Liu, L.; Zhang, R.; Li, D. Mol. Diversity 2016, 20, 897.
[15] Sepúlveda, B.; Astudillo, L.; Rodríguez, J. A.; Yáñez, T.; Theoduloz, C.; Schmeda-Hirschmann, G. Pharmacol. Res. 2005, 52, 429.
[16] Liu, L.; Yan, X. Y.; Gao, Y. Q.; Rao, X. P. Comb. Chem. High Throughput Screen. 2016, 19, 193.
[17] Kang, M. S.; Hirai, S.; Goto, T.; Kuroyanagi, K.; Lee, J. Y.; Uemura, T.; Ezaki, Y.; Takahashi, N.; Kawada, T. Biochem. Biophys. Res. Commun. 2008, 369, 333.
[18] Wada, H.; Kodato, S.; Kawamori, M.; Morikawa, T.; Nakai, H.; Takeda, M.; Saito, S.; Onoda, Y.; Tamaki, H. Chem. Pharm. Bull. 1985, 33, 1472.
[19] Tolmacheva, I. A.; Tarantin, A. V.; Boteva, A. A.; Anikina, L. V.; Tolstikov, A. G. Pharm. Chem. J. 2006, 40, 489.
[20] Mihu, M. R.; Cabral, V.; Pattabhi, R.; Tar, M. T.; Davies, K. P.; Friedman, A. J.; Martinez, L. R.; Nosanchuk, J. D. Antimicrob. Agents. Chemother. 2017, 61, e02020.
[21] Zhao, J.; Gou, S.; Sun, Y.; Yin, R.; Wang, Z. Chemistry 2015, 18, 14276.
[22] Bao, N.; Ou, J. F.; Li, N.; Zou, P.; Sun, J. B.; Chen, L. Eur. J. Med. Chem. 2018, 54, 1.
[23] Naimi, E.; Zhou, A.; Khalili, P.; Wiebe, L. I.; Balzarini, J.; De Clercq, E.; Knaus, E. E. J. Med. Chem. 2003, 46, 995.
[24] Guo, Y.; Wang, Y.; Li, H.; Wang, K.; Wan, Q.; Li, J.; Zhou, Y.; Chen, Y. ACS Med. Chem. Lett. 2018, 9, 502.
[25] Ai, Y.; Kang, F.; Huang, Z.; Xue, X.; Lai, Y.; Peng, S.; Tian, J.; Zhang Y. J. Med. Chem. 2015, 58, 2452.
[26] Xu, S.; Wang, G.; Lin, Y.; Zhang, Y.; Pei, L.; Yao, H.; Hu, M.; Qiu, Y.; Huang, Z.; Zhang, Y.; Xu, J. Bioorg. Med. Chem. Lett. 2016, 26, 2795.
[27] Chen, J.; Wang, T.; Xu, S.; Lin, A.; Yao, H.; Xie, W.; Zhu, Z.; Xu, J. Eur. J. Med. Chem. 2017, 132, 173.
[28] Wang, X.; Pang, F. H.; Huang, L.; Yang, X. P.; Ma, X. L.; Jiang, C. N.; Li, F. Y.; Lei, F. H. Int. J. Mol. Sci. 2018, 19, 3116.
[29] Li, F. Y.; Huang, L.; Li, Q.; Wang, X.; Ma, X. L.; Jiang, C. N.; Duan, W. G.; Lei, F. H. Molecules 2019, 24, 4191.
[30] Li, F. Y.; Wang, X.; Duan, W. G.; Lin, G. S. Molecules 2017, 22, 1087.
[31] Lin, G. S.; Duan, W. G.; Yang, L. X.; Huang, M.; Lei, F. H. Molecules 2017, 22, 193.
[32] Sakuma, T.; Sato, K. US 13/380388, 2012.
[33] Cui, Y. M.; Yasutomi, E.; Otani, Y.; Yoshinaga, T.; Ido, K.; Sawada, K.; Ohwada, T. Bioorg. Med. Chem. Lett. 2008, 18, 5201.
Options
Outlines

/

〈 〉