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Chinese Journal of Organic Chemistry >

2021 , Vol. 41 >Issue 6: 2393 - 2400

DOI: https://doi.org/10.6023/cjoc202101058

ARTICLES

Design, Synthesis and Biological Evaluation of Novel Thiazole-Fused Glaucocalyxin A Derivatives

  • Tao Zhang ,
  • Nianxian Li ,
  • Nanqian Zhou ,
  • Wen Ma ,
  • Haiyuan Wei ,
  • Bingxin Zhang ,
  • Lianghui Chen ,
  • Guangfan Hai ,
  • Yingchao Duan ,
  • Suping Bai
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  • a School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003
    b Department of Ultrasonography, Henan Provincial Peopleʼs Hospital, Zhengzhou 450003
*Corresponding author.E-mail:

Received date: 2021-01-31

  Revised date: 2021-02-26

  Online published: 2021-03-09

Supported by

National Natural Science Foundation of China(21672182); Science and Technology Tackling Key Project of Henan Province(212102311026); National Undergraduate Training Program for Innovation and Entrepreneurship(202010472018)

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Abstract

Glaucocalyxin A (GLA) is an active natural tetracyclic diterpenoid isolated from the traditional Chinese herb Isodon glaucocalyx (maxin) Hara. In this work, a series of thiazole type derivatives based on GLA were designed and prepared. Their antiproliferative activities against six tumor cell lines (HepG2, NCI-H460, JEG-3, K562, HL-60 and Hela) were evaluated in-vitro. The results revealed that the introduction of aminothiazole substructures into A-ring of the GLA could improve their antiproliferative effects significantly. Among them,N-alkyl thiazole derivatives showed remarkably activities to the six tumor cell lines. Especially, compounds6and8presented significant antitumor activities against HL-60 and Hela cell lines with IC50 as low as 0.51 µmol•L –1, which were better than the positive drug adriamycin. The apoptosis morphology and flow cytometry studies indicated that the thiazole-fused GLA derivatives could induce apoptosis of tumor cells.

Key words： glaucocalyxin A; thiazole; antitumor

Cite this article

Tao Zhang , Nianxian Li , Nanqian Zhou , Wen Ma , Haiyuan Wei , Bingxin Zhang , Lianghui Chen , Guangfan Hai , Yingchao Duan , Suping Bai . Design, Synthesis and Biological Evaluation of Novel Thiazole-Fused Glaucocalyxin A Derivatives[J]. Chinese Journal of Organic Chemistry, 2021 , 41(6) : 2393 -2400 . DOI: 10.6023/cjoc202101058

References

[1]
Sharifi-Rad, J.; Ozleyen, A.; Boyunegmez Tumer, T.; Oluwaseun Adetunji, C.; El Omari, N.; Balahbib, A.; Taheri, Y.; Bouyahya, A.; Martorell, M.; Martins, N.. C. Cho, W. Biomolecules 2019, 9,679.
[2]
Wong, A. S. T.; Che, C. M.; Leung, K. W. Nat. Prod. Rep. 2015, 32,256.
[3]
Li, G.; Lou, H. X.. Med. Res. Rev. 2018, 38,1255.
[4]
Rodrigues, T.; Reker, D.; Schneider, P.; Schneider, G. Nat. Chem. 2016, 8,531.
[5]
Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2016, 79,629.
[6]
Zhang, W.; Huang, Q.; Hua, Z. C. Front. Biol. 2010, 5,540.
[7]
Li, D.; Han, T.; Liao, J.; Hu, X.; Xu, S.; Tian, K.; Gu, X.; Cheng, K.; Li, Z.; Hua, H.; Xu, J. Int. J. Mol. Sci. 2016,17.
[8]
Wang, M.; Li, H.; Xu, F.; Gao, X.; Li, J.; Xu, S.; Zhang, D.; Wu, X.; Xu, J.; Hua, H.; Li, D. Eur. J. Med. Chem. 2018, 156,885.
[9]
Xiang, Z.; Wu, X.; Liu, X.; Jin, Y. Nat. Prod. Res. 2014, 28,2221.
[10]
Wang, F. D.; Wang, T.; Wu, A. A.; Ding, L.; Wang, H. Q. Chin. J. Chem. Phys. 2009, 22,275.
[11]
Gao, L. W.; Zhang, J.; Yang, W. H.; Wang, B.; Wang, J. W. Toxicol in Vitro 2011, 25,51.
[12]
Guo, J.; Li, B.; Ma, W.; Pitchakuntla, M.; Jia, Y. Angew. Chem. Int. Ed. 2020, 59,15195.
[13]
Cheng, D. D.; Zhang, Y. X.; Wang, J. M.; Bai, S. P. Chin. J. Org. Chem. 2019, 39,1794.
[14]
Liu, H. C.; Qiao, L. M.; Zheng, W.; Xiang, Z. B.; Chen, H. S.; Yu, S. C.; Zhang, D. Z.; Wang, T.; Zhang, Y. F.; Jin, Y. S. Anti-Cancer Agents Med. Chem. 2020, 20,1241.
[15]
Yang, J.; Liu, Y.; Xue, C.; Yu, W.; Zhang, J.; Qiao, C. Eur. J. Med. Chem. 2014, 86,235.
[16]
Yuan, Y. L.; Ye, D. D.; Liang, H. J.; Zhou, N. Q.; Hai, G. F.; Zhang, Y. X.; Bai, S. P. Planta Med. 2012, 78,589.
[17]
Ren, L.; Wang, J.; Chen, G. Drug Delivery 2019, 26,309.
[18]
Ding, C.; Zhang, Y.; Chen, H.; Yang, Z.; Wild, C.; Chu, L.; Liu, H.; Shen, Q.; Zhou, J. J. Med. Chem. 2013, 56,5048.
[19]
Dahiya, R.; Dahiya, S.; Fuloria, N. K.; Kumar, S.; Mourya, R.; Chennupati, S. V.; Jankie, S.; Gautam, H.; Singh, S.; Karan, S. K.; Maharaj, S.; Fuloria, S.; Shrivastava, J.; Agarwal, A.; Singh, S.; Kishor, A.; Jadon, G.; Sharma, A. Mar. Drugs 2020, 18,329.
[20]
Sharma, P. C.; Bansal, K. K.; Sharma, A.; Sharma, D.; Deep, A. Eur. J. Med. Chem. 2020, 188,112016.
[21]
Ayati, A.; Emami, S.; Moghimi, S.; Foroumadi, A. Future Med. Chem. 2019, 11,1929.
[22]
Lin, Z.; Wang, Z.; Zhou, X.; Zhang, M.; Gao, D.; Zhang, L.; Wang, P.; Chen, Y.; Lin, Y.; Zhao, B.; Miao, J.; Kong, F. Cell Death Dis. 2020, 11,551.
[23]
Qiao, Q.; So, S. S.; Goodnow, R. A. Org. Lett. 2001, 3,3655.
[24]
Yoshio, T.; Tetsuro, F.; Akira, U. Chem. Lett. 1981, 10,1229.
[25]
Liang, H. J.; Zhang, Y. X.; Hai, G. F.; Bai, S. P.; Yuan, Y. L.; Ye, D. D.; Zhou, N. Q. Planta Med. 2012, 78,589.
[26]
Liu, W.; Fan, B.-L.; Guo, H. Y.; Yuan, Y. L.; Liang, H.-J.; Bai, S. P.. Nat. Prod. Res. 2013, 27,1388.
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