Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and Antiproliferative Activity of Isolongifolanone Pyrazoline Derivatives Inducing Intracellular ROS Accumulation

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

A series of new isolongifolanone pyrazoline derivatives were synthesized and characterized by 1H NMR and HRMS methods. The compounds were assessed for their antiproliferative activity against three cancer cell lines (MDA-MB-231, Hela, and HepG2 cells) in vitro. Most of the derivatives showed considerable cytotoxic activity to all three cancer cell lines. Among them, compound 400 exhibited excellent antiproliferative activity with IC50 values of 15.45, 18.52, and 34.4 μM for MDA-MB-231, Hela, and HepG2 cells, respectively. Further mechanistic studies indicated that compound 400 induced apoptosis in HepG2 cells by enhancing the accumulation of intracellular reactive oxygen species (ROS). In summary, we report the synthesis of a new pyrazoline derivative of isolongifolanone (compound 400) that potently induces apoptosis in HepG2 cells by enhancing intracellular ROS production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1.
Fig. 1.
Fig. 2.

Similar content being viewed by others

References

  1. L. A. Torre, F. Bray, R. L. Siegel, et al., CA-Cancer J. Clin., 65(2), 87 – 108 (2015).

    Article  Google Scholar 

  2. S. H. Hassanpour and M. Dehghani, J. Cancer Res. Pract., 4, 127 – 129 (2017).

    Google Scholar 

  3. F. Guerra, A. A. Arbini, and L. Moro, BBA Bioenergetics, 1858(8), 686 – 699 (2017).

    Article  CAS  Google Scholar 

  4. C. A. Lambert, N. Garbacki, and A. C. Colige, Int. J. Biochem. Cell Biol., 91(Part B), 84 – 97 (2017).

  5. D. D. Korablina, N. I. Vorozhtsov, L. A. Sviridova, et al., Pharm. Chem. J., 50(5), 281 – 295 (2016).

    Article  CAS  Google Scholar 

  6. S. Bano, M. S. Alam, K. Javed, et al., Eur. J. Med. Chem., 95, 96 – 103 (2015).

    Article  CAS  Google Scholar 

  7. Z. Ratkoviæ, Z. D. Juraniæ, and T. Stanojkoviæ, Bioorg. Chem., 38, 26 – 32 (2010).

    Article  Google Scholar 

  8. M. Johnson, B. Younglove, L. Lee, et al., Bioorg. Med. Chem. Lett., 17, 5897 – 5901 (2007).

    Article  CAS  Google Scholar 

  9. R. Fioravanti, A. Bolasco, F. Manna, et al., Eur. J. Med. Chem., 45, 6135 – 6138 (2010).

    Article  CAS  Google Scholar 

  10. J. N. Domínguez, J. E. Charris, M. Caparelli, et al., Drug Res., 52(6), 482 – 488 (2002).

    Google Scholar 

  11. B. Kocyigit-Kaymakcioglu, R. G. Aker, K. Tezcan, et al., Med. Chem. Res., 20, 607 – 614 (2011).

    Article  CAS  Google Scholar 

  12. P. Singh, Shaveta, S. Sharma, and R. Bhattil., Bioorg. Med. Chem. Lett., 24(1), 77 – 82 (2014).

    Article  CAS  Google Scholar 

  13. N. A. Hamdy and W. M. El-Senousy, Acta. Pol. Pharm., 70(1), 99 – 110 (2013).

    CAS  PubMed  Google Scholar 

  14. R. Aggarwal, V. Kumar, P. Tyagi, et al., Bioorg. Med. Chem., 14(6), 1785 – 1791 (2006).

    Article  CAS  Google Scholar 

  15. V. K. Tandon, D. B. Yadav, A. K. Chaturvedi, et al., Bioorg. Med. Chem. Lett., 15(13), 3288 – 3291 (2005).

    Article  CAS  Google Scholar 

  16. B. Koçyiðit-Kaymakçýoðlu, N. Beyhan, N. Tabanca, et al., Med. Chem. Res., 24, 3632 – 3644 (2015).

    Article  Google Scholar 

  17. M. F. Khan, M. M. Alam, G. Verma, et al., Eur. J. Med. Chem., 120, 170 – 201 (2016).

    Article  CAS  Google Scholar 

  18. J. Akhtar, A. A. Khan, Z. Ali, et al., Eur. J. Med. Chem., 125, 143 – 189 (2017).

    Article  CAS  Google Scholar 

  19. A. Chauhan, P. K. Sharma, N. Kaushik, et al., Int. J. Pharm. Pharm. Sci., 3 (Suppl. 5), 166 – 176 (2011).

    CAS  Google Scholar 

  20. N. Siddiqui, P. Alam, and W. Ahsan, Arch. Pharm. Chem. Life Sci.,342, 173 – 181 (2009).

    Article  CAS  Google Scholar 

  21. J. Chen, W. Li, H. Yao, et al., Fitoterapia,103, 231 – 241(2015).

    Article  CAS  Google Scholar 

  22. J. Rui, T. Cai, J. L. Yang, et al., J. Nanjing Forest Univ.: Nat. Sci. Ed., 41(1), 149 – 155 (2017); https://doi.org/https://doi.org/10.3969/j.issn.1000–2006.2017.01.023

  23. C. H. Ma, C. L. Wu, Y. Y. Wang, et al., Chin. J. Org. Chem., 39 (3), 821 (2019); https://doi.org/https://doi.org/10.6023/cjoc201807022

  24. M. K. Bao, S. S. Xiong, M. Z. Cao, et al., Chin. J. Org. Chem.,34, 2130 – 2134 (2014); https://doi.org/https://doi.org/10.6023/cjoc201404021.

  25. J. Rui, J. L. Yang, J. F. Hang, et al., Chin. J. Org. Chem.,36, 2183 – 2190 (2016); https://doi.org/https://doi.org/10.6023/cjoc201603023.

  26. Y. Y. Wang, W. Gu, Y. Shan, et al., Bioorg. Med. Chem. Lett., 27, 2360 – 2363 (2017).

    Article  CAS  Google Scholar 

  27. M. K. Bao, Y. Q. Yang, W. Gu, et al., Chin. J. Org. Chem.,34, 2146 – 2151 (2014); https://doi.org/https://doi.org/10.6023/cjoc201404049.

  28. N. Sun, X. Wang, Z. B. Ding, et al., Chin. J. Org. Chem.,36, 2489 – 2495 (2016); https://doi.org/https://doi.org/10.6023/cjoc201604042.

  29. J. L. Yang, J. Rui, X. Xu, et al., RSC Adv.,6, 111760 (2016).

    Article  CAS  Google Scholar 

  30. J. L. Yang, H.J. Xu, X. Xu, et al., Dyes Pigments, 128, 75 – 83 (2016).

    Article  CAS  Google Scholar 

  31. P. Ahmad, H. Woo, K. Jun, et al., Bioorg. Med. Chem.,24, 1898–1908 (2016).

    Article  CAS  Google Scholar 

  32. R. Sakthivel, D. S. Malar, and K. P. Devi, Biomed. Pharmacother.,105, 742 – 752 (2018).

    Article  CAS  Google Scholar 

  33. L. S. McLean, L. Crane, G. Baziard-Mouysset, et al., Pharmacol. Rep.,66, 937 – 945 (2014).

    Article  CAS  Google Scholar 

  34. M. Zhu, J. Wang, J. Xie, et al., Eur. J. Med. Chem.,157, 1395 – 1405 (2018).

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The present study was supported by National Natural Sciences Foundation of China (project no. 31470592), Major Project of the Jiangsu Province University of Natural Sciences (no. 14KJ220001), and Open Funding of the Jiangsu Key Laboratory of Biomass Energy and Materials (project no. JSBEM2014010).

Author information

Authors and Affiliations

  1. College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China

    Chenliang Wu, Yunyun Wang & Shifa Wang

  2. Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China

    Shifa Wang

Authors
  1. Chenliang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yunyun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shifa Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shifa Wang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, C., Wang, Y. & Wang, S. Synthesis and Antiproliferative Activity of Isolongifolanone Pyrazoline Derivatives Inducing Intracellular ROS Accumulation. Pharm Chem J 53, 706–712 (2019). https://doi.org/10.1007/s11094-019-02067-z

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-019-02067-z

Keywords

Search

Navigation