Skip to main content

Synthesis and Antiproliferative Activity of Some New Coumarin Derivatives Derived from 8-Hydroxycoumarin

Abstract

A new series of coumarin-derived molecules have been synthesized and evaluated for their anticancer activity against human hepatocellular liver carcinoma cell line (HepG2). Compound (IX) showed the least IC50 values in MTT colorimetric assay and significantly inhibited topoisomerase IIβ. DNA flow cytometry assay of compound (IX) revealed cell cycle arrest at G2/M phase and activation of apoptosis as verified by changes in cell cycle kinetics. Further mechanism of apoptosis showed that, compound (IX) induced cell apoptosis probably through the intrinsic mitochondrial pathway of apoptosis. This mechanistic pathway was confirmed by a significant increase in the level of p53, Bax and decrease in the level of Bcl-2 compared to control.

This is a preview of subscription content, access via your institution.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.

REFERENCES

  1. Siegel, R.L., Jemal, A., Wender, R.C., Gansler, T., Ma, J., and Brawley, O.W., CA Cancer J. Clin., 2018, vol. 68, pp. 329–339. https://doi.org/10.3322/caac.21460

    Article  PubMed  Google Scholar 

  2. Zhou, F., Shang, W., Yu, X., and Tian, J., Med. Res. Rev., 2018, vol. 38, pp. 741–767. https://doi.org/10.1002/med.21455

    CAS  Article  PubMed  Google Scholar 

  3. Pommier, Y., Leo, E., Zhang, H., Marchand, C., Chem. Biol., 2010, vol. 17, pp. 421–433. https://doi.org/10.1016/j.chembiol.2010.04.012

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Abdelhaleem, E.F., Abdelhameid, M.K., Kassab, A.E., and Kandeel, M.M., Eur. J. Med. Chem., 2018, vol. 143, pp. 1807–1825. https://doi.org/10.1016/j.ejmech.2017.10.075

    CAS  Article  PubMed  Google Scholar 

  5. Nitiss, J.L., Nat. Rev. Cancer, 2009, vol. 9, pp. 338–350. https://doi.org/10.1038/nrc2607

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Wang, N., Zhu, M., Tsao, S.-W., Man, K., Zhang, Z., and Feng, Y., Mol. Cancer, 2013, vol. 12, pp. 119. https://doi.org/10.1186/1476-4598-12-119

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Sudan, S. and Rupasinghe, H.V., Anticancer Res., 2014, vol. 34, pp. 1691–1699. http://ar.iiarjournals.org/content/34/4/1691.abstract.

    CAS  PubMed  Google Scholar 

  8. Elmore, S., Toxicol. Pathol., 2007, vol. 35, pp. 495–516. https://doi.org/10.1080/01926230701320337

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Rashad, M.S., Georgey, H.H., George, R.F., and Abdel-Gawad, N.M., Future Med. Chem., 2018, vol. 10, pp. 1649–1664. https://doi.org/10.4155/fmc-2018-0068

    CAS  Article  PubMed  Google Scholar 

  10. Kim, R., Emi, M., and Tanabe, K., Cancer Biol. Ther., 2005, vol. 4, pp. 924–933. https://doi.org/10.4161/cbt.4.9.2101

    CAS  Article  PubMed  Google Scholar 

  11. Abdelhameid, M.K., Zaki, I., Mohammed, M.R., and Mohamed, K.O., Bioorg. Chem., 2020, vol. 101, pp. 103995–104007. https://doi.org/10.1016/j.bioorg.2020.103995

    CAS  Article  PubMed  Google Scholar 

  12. Zaki, I., Abdelhameid, M.K., El-Deen, I.M., Abdel Wahab, A.H.A., Ashmawy, A.M., and Mohamed, K.O., Eur. J. Med. Chem., 2018, vol. 156, pp. 563–579. https://doi.org/10.1016/j.ejmech.2018.07.003

    CAS  Article  PubMed  Google Scholar 

  13. Liu, Y.-P., Yan, G., Xie, Y.-T., Lin, T.-C., Zhang, W., Li, J., Wu, Y.-J., Zhou, J.-Y., and Fu, Y.-H., Bioorg. Chem., 2020, vol. 97, pp. 103699–103713. https://doi.org/10.1016/j.bioorg.2020.103699

    CAS  Article  PubMed  Google Scholar 

  14. Swain, B., Angeli, A., Singh, P., Supuran, C.T., and Arifuddin, M., Bioorg. Med. Chem., 2020, vol. 28, pp. 115586–115597. https://doi.org/10.1016/j.bmc.2020.115586

    CAS  Article  PubMed  Google Scholar 

  15. Ahmed, E.Y., Abdel Latif, N.A., El-Mansy, M.F., Elserwy, W.S., and Abdelhafez, O.M., Bioorg. Med. Chem., 2020, vol. 28, pp. 115328–115338. https://doi.org/10.1016/j.bmc.2020.115328

    CAS  Article  PubMed  Google Scholar 

  16. Zhang, L. and Xu, Z., Eur. J. Med. Chem., 2019, vol. 181, pp. 111587. https://doi.org/10.1016/j.ejmech.2019.111587

    CAS  Article  PubMed  Google Scholar 

  17. Manolov, I., Maichle-Moessmer, C., and Danchev, N., Eur. J. Med. Chem., 2006, vol. 41, pp. 882–890. https://doi.org/10.1016/j.ejmech.2006.03.007

    CAS  Article  PubMed  Google Scholar 

  18. Wang, J., Lu, M.L., Dai, H.L., Zhang, S.P., Wang, H.X., and Wei, N., Braz. J. Med. Biol. Res., 2015, vol. 48, pp. 245–253. https://doi.org/10.1590/1414-431x20144074

    CAS  Article  PubMed  Google Scholar 

  19. Prasad, K.N., Xie, H., Hao, J., Yang, B., Qiu, S., Wei, X., Chen, F., and Jiang, Y., Food Chem., 2010, vol. 118, pp. 62–66. https://doi.org/10.1016/j.foodchem.2009.04.073

    CAS  Article  Google Scholar 

  20. Hejchman, E., Taciak, P., Kowalski, S., Maciejewska, D., Czajkowska, A., Borowska, J., Śladowski, D., and Młynarczuk-Biały, I., Pharmacol. Rep., 2015, vol. 67, pp. 236–244. https://doi.org/10.1016/j.pharep.2014.09.008

    CAS  Article  PubMed  Google Scholar 

  21. Nasr, T., Bondock, S., and Youns, M., Eur. J. Med. Chem., 2014, vol. 76, pp. 539–548. https://doi.org/10.1016/j.ejmech.2014.02.026

    CAS  Article  PubMed  Google Scholar 

  22. Zhao, P., Chen, L., Li, L.-H., Wei, Z.-F., Tong, B., Jia, Y.-G., Kong, L.-Y., Xia, Y.-F., and Dai, Y., BMC Cancer, 2014, vol. 14, pp. 987–1005. https://doi.org/10.1186/1471-2407-14-987

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. El-Deen, I., Elgareib, M.S., Mahdy, A.R., and Al-Saleem, M.S., Mens Agitat, 2018, vol. 13, pp. 1–5.

    Google Scholar 

  24. Moustafa, A.M.Y. and Bakare, S.B., Res. Chem. Intermed., 2019, vol. 45, pp. 3895–3912. https://doi.org/10.1007/s11164-019-03827-y

    CAS  Article  Google Scholar 

  25. Rahman, A.U., Medrano, M.A., and Mittal, O., Recl. Trav. Chim. Pays-Bas, 1960, vol. 79, pp. 188–192.

    CAS  Article  Google Scholar 

  26. Menezes, J.C. and Diederich, M., Future Med. Chem., 2019, vol. 11, pp. 1057–1082. https://doi.org/10.4155/fmc-2018-0375

    CAS  Article  PubMed  Google Scholar 

  27. Mohamed, K.O., Zaki, I., El-Deen, I.M., and Abdelhameid, M.K., Bioorg. Chem., 2019, vol. 84, pp. 399–409. https://doi.org/10.1016/j.bioorg.2018.12.007

    CAS  Article  PubMed  Google Scholar 

  28. Wei, H., Ruthenburg, A.J., Bechis, S.K., and Verdine, G.L., J. Biolog. Chem., 2005, vol. 280, pp. 37041–37047. https://doi.org/10.1074/jbc.M506520200

    CAS  Article  Google Scholar 

Download references

Funding

This work was funded by the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Islam Zaki.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving animals or human participants performed by any of the authors.

Conflict of Interests

The authors report no conflicts of interest.

Supplementary Information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zaki, I., El-Sayed, ES.H. & Radwan, E.M. Synthesis and Antiproliferative Activity of Some New Coumarin Derivatives Derived from 8-Hydroxycoumarin. Russ J Bioorg Chem 47, 514–523 (2021). https://doi.org/10.1134/S106816202102028X

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S106816202102028X

Keywords:

  • coumarin
  • MTT
  • cell cycle analysis
  • annexin V
  • p53
  • Bax