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Chinese Journal of Organic Chemistry >

2019 , Vol. 39 >Issue 10: 2860 - 2866

DOI: https://doi.org/10.6023/cjoc201902024

ARTICLES

Syntheses and Property Evaluation of N-Salicylaldehyde Hydrazone Modified 11-Azaartemisinins and Their Derivatives

  • Sicong Li, ,
  • Shaocong Ji, ,
  • Liang Zhao, ,
  • Xiaoyu Liao, ,
  • Chuanfeng Liu, ,
  • Haodong Tang, ,
  • Zhengning Shu, ,
  • Peng Yang, ,
  • Yuehu Pei,
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  • a Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016
    b School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016

Received date: 2019-02-22

  Revised date: 2019-04-29

  Online published: 2019-06-06

Supported by

Project supported by the Natural Science Foundation of Liaoning Province(20180550874)

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Abstract

N-Salicylaldehyde hydrazone modified 11-azaartemisinins and their deoxy analogues were designed and synthesized. By using various techniques including UV-vis, fluorescence, NMR as well as molecular modeling, the conformations of (3R,5aS,6R,8aS,9R,12S,12aR)-11-(((E)-2-hydroxy-5-(4-hydroxy-3-((E)-(((3R,5aS,6R,8aS,9R,12R,12aR)-3,6,9-trimethyl-10- oxodecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-11(12H)-yl)imino)methyl)benzyl)benzylidene)amino)-3,6,9-trimethyldecahydro-3,12-epoxy[1,2]dioxepino[4,3-i]isoquinolin-10(3H)-one (3) was analyzed, the binding behavior between 3 and hemin was measured, and the solubility-enhancing property of 3 by calix[4]carbazole was evaluated. The results show that the intramolecular hydrogen binding between the N atom of Schiff base in N-salicylaldehyde hydrazone bond and the OH favors the formation of tweezer-like conformation of 3, which enables it to interact with hemin in 1∶1 ratio. Moreover, the poor solubility of 3 in water could be enhanced due to its interaction with calix[4]carbazole, which pave the way for the further evaluation of the bioactivities of 3 in the future.

Key words： macrocycle; molecular recognition; carbazole; artemisinin

Cite this article

Sicong Li, , Shaocong Ji, , Liang Zhao, , Xiaoyu Liao, , Chuanfeng Liu, , Haodong Tang, , Zhengning Shu, , Peng Yang, , Yuehu Pei, . Syntheses and Property Evaluation of N-Salicylaldehyde Hydrazone Modified 11-Azaartemisinins and Their Derivatives[J]. Chinese Journal of Organic Chemistry, 2019 , 39(10) : 2860 -2866 . DOI: 10.6023/cjoc201902024

References

[1] (a) Tu, Y. Y . Artemisia Annua and Artemisinin Drugs, Chemical Industry Press, Beijing, 2009 (in Chinese).
[1] ( 屠呦呦 , 青蒿及青蒿素类药物, 化学工业出版社, 北京, 2009.)
[1] (b) Chang, Z . Sci. China Life Sci. 2016,59, 81.
[1] (c) Li, G. Q.; Li, Y.; Li, Z. L.; Zeng,, M. Y . Artemisinin Antimalarial Drug, Science Press, Beijing, 2015 (in Chinese).
[1] ( 李国桥, 李英, 李泽琳, 曾美怡 , 青蒿素类抗疟药, 科学出版社, 北京, 2015.)
[2] (a) Eckstein L. U.; Webb, R J.; van Goethem, I. D. A.; East J. M.; Lee A. G.; Kimura M.; O'Neill P. M.; Bray P. G.; Ward S. A.; Krishna S. Nature 2003, 424, 957.
[2] (b) O'Neill P. M.; Posner, G. H. J. Med. Chem. 2004, 47, 2945.
[2] (c) Utzinger, J.; Xiao, S. H.; Tanner, M.; Keiser, J . Curr. Opin. Invest. Drugs 2004, 47, 105
[3] You Q. D. Medicinal Chemistry, 1st ed., Chemical Industry Press, Beijing, 2005, p. 402 (in Chinese).
[3] ( 尤启冬 , 药物化学(第一版), 化学工业出版社, 2005, p. 402)
[4] (a) Phyo, a. P.; Nkhoma, S.; Stepniewska, K.; Ashley, E. A.; Nair, S.; McGready, R.; ler Moo, C.; Al-Saai, S.; Dondorp, A. M.; Lwin, K. M.; Singhasivanon, P.; Day, N. P.; White, N. J.; Anderson, T. J.; Nosten, F . Lancet. 2008, 359, 1960.
[4] (b) Noedl H.; Se Y.; Schaecher K.; Smith B. L.; Socheat D.; Fukuda, M. M. N. Engl. J. Med. 2008, 359, 2619.
[5] Singh C.; Verma V. P.; Hassam M.; Singh A. S.; Naikade N. K.; Puri S. K. J Med. Chem. 2014, 57, 2489.
[6] (a) Sun, Z. J . M.S. Thesis, Guangdong Pharmaceutical University, Guangzhou, 2008 (in Chinese).
[6] ( 孙政进 , 硕士论文, 广东药学院, 广州, 2008.)
[6] (b) Chen, Y. X.; Yu, P. L.; Li, Y.; Ji,, R.Y . Acta Chim. Sinica 1985, 20, 470 (in Chinese).
[6] ( 陈一心, 虞佩琳, 李英, 嵇汝运 , 化学学报, 1985, 20, 470.)
[7] (a) Yang, Z.-Z.; Chen, Y.; Li, G.; Tian, Z.; Zhao, L.; Wu, X.; Ma, Q.; Liu, M.-Z.; Yang, P. . Chem.-Eur. J. 2018, 24, 6087.
[7] (b) Zhao L.; Kang L.; Chen Y.; Li G.; Wang L.; Hu C.; Yang, P. Spectrochim. Acta, Part A 2018, 193, 276.
[7] (c) Yang, P.; Jian, Y.; Zhou, X.; Li, G.; Deng, T.; Shen, H.-Y.; Yang, Z.-Z.; Tian, Z.-M . J. Org. Chem. 2016, 88, 10751
[8] Yao H.; Sun J. N.; Ke H.; Yang L. P.; Li J. R, Jiang, W . Chin. J. Org. Chem. 2017, 37, 603 (in Chinese).
[8] ( 姚欢, 孙娇囡, 柯华, 杨留攀, 李加荣, 蒋伟 , 有机化学, 2017, 37, 603.)
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