Citation: Du Chuanqian, Xie Baohua, He Ming, Hu Zhiye, Liu Yu, He Xue, Liu Fanyu, Cheng Chen, Zhou Hai-Bing, Huang Shengtang, Dong Chun'e. Design, Synthesis and Biological Evaluation of Pyrano[2, 3-b]-naphthoquinone Derivatives as Acetylcholinesterase Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2020, 40(7): 2035-2044. doi: 10.6023/cjoc202002039 shu

Design, Synthesis and Biological Evaluation of Pyrano[2, 3-b]-naphthoquinone Derivatives as Acetylcholinesterase Inhibitors

  • Corresponding author: Zhou Hai-Bing, zhouhb@whu.edu.cn Huang Shengtang, cdong@whu.edu.cn Dong Chun'e, cdong@whu.edu.cn
  • These authors contributed equally to this work
  • Received Date: 27 February 2020
    Revised Date: 11 April 2020
    Available Online: 23 April 2020

    Fund Project: the Open Project of the Diabetes Key Laboratory of Hubei University of Science and Technology 2020-21XZ002the National Natural Science Foundation of China 81773557the Major Project of Technology Innovation Program of Hubei Province 2018ACA123Project supported by the National Natural Science Foundation of China (No. 81773557), the Major Project of Technology Innovation Program of Hubei Province (No. 2018ACA123) and the Open Project of the Diabetes Key Laboratory of Hubei University of Science and Technology (No. 2020-21XZ002)

Figures(5)

  • A novel synthetic methodology was developed and a series of pyrano[2, 3-b]naphthoquinone derivatives were designed and synthesized in excellent yields. Most of these compounds showed effective anti-AChE activities and high selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Among them, (2-Amino-4-(3-cyanophenyl)-5, 10-dioxo-5, 10-dihydro-4H-benzo[g]chromene-3-carbonitrile) (3n) was significantly potent, with an IC50 value of 1.22 μmol/L for AChE, which was 164-fold higher than butyrylcholinesterase (BuChE) in vitro. Moreover, molecular modeling provides valuable information for understanding the potency and selectivity of this kind of compounds for AChE. Consequently, these potent and highly selective AChE inhibitors are potential leads for development of the drug for treatment of Alzheimer's disease.
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    1. [1]

      Bondi, M. W.; Edmonds, E. C.; Salmon, D. P. J. Int. Neuropsychol. Soc. 2017, 23, 818.  doi: 10.1017/S135561771700100X

    2. [2]

      Cuetos, F.; Herrera, E.; Ellis, A. W. Neuropsychologia 2010, 48, 3329.  doi: 10.1016/j.neuropsychologia.2010.07.017

    3. [3]

      Alzheimer's Association Alzheimers Dement. 2019, 15, 321.

    4. [4]

      Wimo, A.; Guerchet, M.; Ali, G. C.; Wu, Y. T.; Prina, A. M.; Winblad, B.; Jönsson, L.; Liu, Z.; Prince, M. Alzheimers Dement. 2016, 13, 1.

    5. [5]

      Scarpini, E.; Scheltens, P.; Feldman, H. Lancet Neurol. 2003, 2, 539.  doi: 10.1016/S1474-4422(03)00502-7

    6. [6]

      Fan, L.; Mao, C.; Hu, X.; Zhang, S.; Yang, Z.; Hu, Z.; Sun, H.; Fan, Y.; Dong, Y.; Yang, J.; Shi, C.; Xu, Y. Front Neurol 2020, 10, 1312.  doi: 10.3389/fneur.2019.01312

    7. [7]

      Contestabile, A. Behav. Brain Res. 2011, 221, 334.  doi: 10.1016/j.bbr.2009.12.044

    8. [8]

      Enz, A.; Amstutz, R.; Boddeke, H.; Gmelin, G.; Malanowski, J. Prog. Brain Res. 1993, 98, 431.  doi: 10.1016/S0079-6123(08)62429-2

    9. [9]

      Davies, P.; Maloney, A. J. Lancet 1976, 2, 1403.

    10. [10]

      Babu, M. A.; Lakshmi, M.; Vasanthanathan, P. G.; Kaskhedikar, S. Indian J. Pharm. Sci. 2005, 67, 1.

    11. [11]

      Peauger, L.; Azzouz, R.; Gembus, V.; Ţînţaş, M. L.; Sopková-de Oliveira Santos, J.; Bohn, P.; Papamicaël, C.; Levacher, V. J. Med. Chem. 2017, 60, 5909.
       

    12. [12]

      (a) Auld, D. S.; Kornecook, T. J.; Bastianetto, S.; Quirion, R. Prog. Neurobiol. 2002, 68, 209.
      (b) Mohammad, D.; Chan, P.; Bradley, J.; Lanctôt, K.; Herrmann, N. Expert Opin. Drug Saf. 2017, 16, 1009.

    13. [13]

      (a) Smith, D. A. Am. J. Health-Syst. Pharm. 2009, 66, 899.
      (b) Herrmann, N.; Chau, S. A.; Kircanski, I.; Lanctôt, K. L. Drugs 2011, 71, 2031.
      (c) Misra, S.; Medhi, B. Neurol. Sci. 2013, 34, 831.

    14. [14]

      Brewster, J. T.; Dell'Acqua, S.; Thach, D. Q.; Sessler, J. L. ACS Chem. Neurosci. 2019, 10, 155.  doi: 10.1021/acschemneuro.8b00517

    15. [15]

      (a) Luo, Z.; Sheng, J.; Sun, Y.; Lu, C.; Yan, J.; Liu, A.; Luo, H. B.; Huang, L.; Li, X. J. Med. Chem. 2013, 56, 9089.
      (b) Graham, W. V.; Bonito-Oliva, A.; Sakmar, T. P. Annu. Rev. Med. 2017, 68, 413.

    16. [16]

      Kuhl, D. E.; Koeppe, R. A.; Snyder, S. E.; Minoshima, S.; Frey, K. A.; Kilbourn, M. R. Ann. Neurol. 2006, 59, 13.  doi: 10.1002/ana.20672

    17. [17]

      Akiko, K. J.; Todd, E.; Keith, D. G.; Abdelrahman, S. M.; Mi, H. L.; Sylvie, G. T. Chem. Sci. 2013, 4, 4137.  doi: 10.1039/c3sc51902c

    18. [18]

      Li, S. Y.; Jiang, N.; Xie, S. S.; Wang, K. D.; Wang, X. B.; Kong, L. Y. Org. Biomol. Chem. 2014, 12, 801.  doi: 10.1039/C3OB42010H

    19. [19]

      Xie, S. S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K. D.; Lan, J. S.; Li, Z. R.; Kong, L. Y. Eur. J. Med. Chem. 2015, 95, 153.  doi: 10.1016/j.ejmech.2015.03.040

    20. [20]

      Demir Özkay, Ü.; Can, Ö. D.; Sağlık, B. N.; Acar Çevik, U.; Levent, S.; Özkay, Y.; Ilgın, S.; Atlı, Ö. Bioorg. Med. Chem. Lett. 2016, 26, 5387.  doi: 10.1016/j.bmcl.2016.10.041

    21. [21]

      Azzouz, R.; Peauger, L.; Gembus, V.; Ţînţaş, M. L.; Sopková-de Oliveira Santos, J.; Papamicaël, C.; Levacher, V. Eur. J. Med. Chem. 2018, 145, 165.  doi: 10.1016/j.ejmech.2017.12.084

    22. [22]

      Singh, M.; Silakari, O. RSC Adv. 2016, 6, 108411.  doi: 10.1039/C6RA17678J

    23. [23]

      Zheng, J.; He, M.; Xie, B.; Yang, L.; Hu, Z.; Zhou, H. B.; Dong, C. Org. Biomol. Chem. 2018, 16, 472.  doi: 10.1039/C7OB02794J

    24. [24]

      Martín-Acosta, P.; Haider, S.; Amesty, Á.; Aichele, D.; Jose, J.; Estévez-Braun, A. Eur. J. Med. Chem. 2018, 144, 410.  doi: 10.1016/j.ejmech.2017.12.058

    25. [25]

      Wang, X. H.; Zhang, X. H.; Tu, S. J.; Shi, F.; Zou, X.; Yan, S.; Han, Z. G.; Hao, W. J.; Cao, X. D.; Wua, S. S. J. Heterocycl. Chem. 2009, 46, 832.  doi: 10.1002/jhet.153

    26. [26]

      Khan, N.; Pal, S.; Karamthulla, S.; Choudhury, L. H. RSC Adv. 2015, 45, 3732.
       

    27. [27]

      Ellman, G. L.; Courtney, K. D.; Andres, V. Jr; Feather-Stone, R. M. Biochem. Pharmacol. 1961, 7, 88.  doi: 10.1016/0006-2952(61)90145-9

    28. [28]

      Maleki, B.; Babaee, S.; Tayebee, R. Appl. Organomet. Chem. 2015, 29, 408.  doi: 10.1002/aoc.3306

    29. [29]

      Sameem, B.; Saeedi, M.; Mahdavi, M.; Nadri, H.; Moghadam, F. H.; Edraki, N.; Khan, M. I.; Amini, M. Bioorg. Med. Chem. 2017, 25, 3980.
       

    30. [30]

      Czarnecka, K.; Chufarova, N.; Halczuk, K.; Maciejewska, K.; Girek, M.; Skibiński, R.; Jończyk, J.; Bajda, M.; Kabziński, J.; Majsterek, I.; Szymański, P. Eur. J. Med. Chem. 2018, 145, 760.  doi: 10.1016/j.ejmech.2018.01.014

    31. [31]

      Dgachi, Y.; Sokolov, O.; Luzet, V.; Godyń, J.; Panek, D.; Bonet, A.; Martin, H.; Iriepa, I.; Moraleda, I.; García-Iriepa, C.; Janockova, J.; Richert, L.; Soukup, O.; Malawska, B.; Chabchoub, F.; Marco- Contelles, J.; Ismaili, L. Eur. J. Med. Chem. 2017, 126, 576.  doi: 10.1016/j.ejmech.2016.11.050

    32. [32]

      Eghtedari, M.; Sarrafi, Y.; Nadri, H.; Mahdavi, M.; Moradi, A.; Homayouni Moghadam, F.; Emami, S.; Firoozpour, L.; Asadipour, A.; Sabzevari, O.; Foroumadi, A. Eur. J. Med. Chem. 2017, 128, 237.
       

    33. [33]

      Kavita, J.; Saikat, C.; Kuntal, P.; Kalpataru, D. New J. Chem. 2019, 43, 1299.  doi: 10.1039/C8NJ04219E

    34. [34]

      Aniruddha, D.; Nagaraj, A.; Amarajothi, D.; Shyam, B. Microporous Mesoporous Mater. 2019, 284, 459.  doi: 10.1016/j.micromeso.2019.04.057

    35. [35]

      Li, C. X.; Zhong, D. D.; Huang, X. Q.; Shen, G. D.; Li, Q.; Du, J. Y.; Li, Q. L.; Wang, S. N.; Li, J. K.; Dou, J. M. New J. Chem. 2019, 43, 5813.  doi: 10.1039/C8NJ06460A

    36. [36]

      Guo, F.; Su, C. H.; Chu, Z. P.; Zhao, M. H. J. Solid State Chem. 2019, 277, 25.  doi: 10.1016/j.jssc.2019.05.036

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