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Design, Synthesis, Molecular Docking and Biological Activity of New Piperidine and Piperazine Derivatives of Dichloroacetate as Potential Anticancer Agents

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Pharmaceutical Chemistry Journal Aims and scope

Dichloroacetate (DCA) is a small anticancer agent acting through inhibition of pyruvate dehydrogenase kinases (PDKs) and preventing proliferation of tumor growth. In this study, a series of new piperidine and piperazine derivatives of DCA were designed and subjected to molecular docking analysis. Based on the docking results, nine compounds with a lowest binding energy and better interaction with PDK isoenzymes were selected and synthesized. The cytotoxic activities of the synthesized compounds were evaluated against HT-29 and MCF7 human cancer cell lines. These compounds showed moderate potency and much higher anticancer activity than DCA. The most active compound of the series (f1) showed IC50 value of 7.79 μM against HT-29 cell line.

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References

  1. Y. Yang, P. Shang, C. Cheng, et al., Eur. J. Med. Chem., 45(9), 4300 – 4306 (2010).

    Article  CAS  Google Scholar 

  2. M. Abdelmalak, A. Lew, R. Ramezani, et al., Mol. Genet. Metab., 109(2), 139 – 143 (2013).

    Article  CAS  Google Scholar 

  3. K. Hans H., K. Taeho, K. Euiyong, et al., IBC, 2009(1), 7 (2009).

  4. I. Papandreou, T. Goliasova, and N. C. Denko, Int. J. Cancer., 128(5), 1001 – 1008 (2011).

    Article  CAS  Google Scholar 

  5. K. M. Popov, FEBS Lett., 419(2 – 3), 197 – 200 (1997).

  6. P. Wells, G. Moore, D. Rabin, et al., Diabetologia, 19(2), 109 – 113 (1980).

    Article  CAS  Google Scholar 

  7. G. R. Bebernitz, T. D. Aicher, J. L. Stanton, et al., J. Med. Chem., 43(11), 2248 – 2257 (2000).

    Article  CAS  Google Scholar 

  8. R. M. Bersin and P. W. Stacpoole, Am. Heart J., 134(5), 841 – 855 (1997).

    Article  CAS  Google Scholar 

  9. J.-C. Preiser, D. Moulart, and J. L. Vincent, Circ. Shock, 30(3), 221 – 228 (1990).

    CAS  PubMed  Google Scholar 

  10. S. Bonnet, S. L. Archer, J. Allalunis-Turner, et al., Cancer Cell, 11, 37e51 (2007).

    Article  Google Scholar 

  11. J. Y. Wong, G. S. Huggins, M. Debidda, et al., Gynecol. Oncol., 109(3), 394 – 402 (2008).

    Article  CAS  Google Scholar 

  12. W. Cao, S. Yacoub, K. T. Shiverick, et al., Prostate, 68(11), 1223 – 1231 (2008).

    Article  CAS  Google Scholar 

  13. D. Heshe, S. Hoogestraat, C. Brauckmann, et al., Cancer Chemother. Pharmacol., 67(3), 647 – 655 (2011).

    Article  CAS  Google Scholar 

  14. Y. Chen, R. Cairns, I. Papandreou, et al., PloS One, 4(9), e7033 (2009).

    Article  Google Scholar 

  15. K. Anderson, J. Jajeh, P. Guinan, et al., Anticancer Res., 29(11), 4579 – 4588 (2009).

    CAS  PubMed  Google Scholar 

  16. S. Shahrzad, K. Lacombe, U. Adamcic, et al., Cancer Lett., 297(1), 75 – 83 (2010).

    Article  CAS  Google Scholar 

  17. L. B. Chen, Ann. Rev. Cell Biol., 4(1), 155 – 181 (1988).

    Article  CAS  Google Scholar 

  18. H. W. R. O. P. H. Protein Data Bank and H. D. A. F; http://Www.Rcsb.Org.

  19. M. Fereidoonnezhad, Z. Faghih, A. Mojaddami, et al., Indian J. Pharm. Educ. Res., 50(2s), S32-S38 (2016).

    CAS  Google Scholar 

  20. H. H. K, T. K., E. K., et al., Mitochondrial Warburg Effect: A Cancer Enigma, IBC, 2009(1), 7 (2009).

  21. M. Fereidoonnezhad, Z. Faghih, A. Mojaddami, et al., J. Sci. Islam. Rep. Iran, 27 (1), 39 – 49 (2016).

    Google Scholar 

  22. T. Li, Y. Yang, C. Cheng, et al., Bioorg. Med. Chem. Lett., 22(23), 7268 – 7271 (2012).

    Article  CAS  Google Scholar 

  23. M. Fereidoonnezhad, Z. Faghih, E. Jokar, et al., Trends Pharm. Sci., 2016(2), 159 (2016).

    Google Scholar 

  24. D. L. Mobley and K. A, Dill, Structure, 17(4), 489 – 498 (2009).

    Article  CAS  Google Scholar 

  25. A. Mojaddami, A. Sakhteman, M. Fereidoonnezhad, et al., Res. Pharm. Sci., 12(1), 21. (2017).

    Article  Google Scholar 

  26. S. Zare, M. Fereidoonnezhad, D. Afshar, et al., Comput. Biol. Chem., 67, 22 – 37 (2017).

    Article  CAS  Google Scholar 

  27. B. Hemmateenejad, S. M. H. Tabaei, and F. Namvaran, J. Iran. Chem. Soc. 4, 481 – 481 (2007).

    CAS  Google Scholar 

  28. N. Edraki, A. Iraji, O. Firuzi, et al., J. Iran. Chem. Soc., 13, 2163–2171 (2016).

    Article  CAS  Google Scholar 

  29. F. Wang and Y. J. Ren, J. Iran Chem Soc., 13, 1155 – 1166 (2016).

    Article  CAS  Google Scholar 

  30. M. Fereidoonnezhad, B. Kaboudin, T. Mirzaee, et al., Organometallics. 36(9), 1707 – 1717 (2017).

    Article  CAS  Google Scholar 

  31. M. Fereidoonnezhad, M. Niazi, Z. Ahmadipour, et al., Eur. J. Inorg. Chem., 2017, 2247 (2017).

    Article  CAS  Google Scholar 

  32. M. Fereidoonnezhad, M. Niazi, M. Shahmohammadi Beni, et al., ChemMedChem., 12(6), 456 – 465 (2017).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank the Department of Medicinal Chemistry, Ahvaz Jundishapur University of Medical Sciences and the Marine Pharmaceutical Science Research Center, Ahvaz Jundishapur University of Medical Sciences (Ahvaz, Iran) for support and help in performing this research.

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Authors and Affiliations

  1. Department of Chemistry, Khuzestan Science and Research Branch, Islamic Azad University, Ahvaz, Iran

    Elham Manouchehrizadeh

  2. Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran

    Elham Manouchehrizadeh, Azar Mostoufi & Elham Tahanpesar

  3. Marine Pharmaceutical Science Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Azar Mostoufi

  4. Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Masood Fereidoonnezhad

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  1. Elham Manouchehrizadeh
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  2. Azar Mostoufi
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  4. Masood Fereidoonnezhad
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Correspondence to Azar Mostoufi.

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Manouchehrizadeh, E., Mostoufi, A., Tahanpesar, E. et al. Design, Synthesis, Molecular Docking and Biological Activity of New Piperidine and Piperazine Derivatives of Dichloroacetate as Potential Anticancer Agents. Pharm Chem J 54, 148–153 (2020). https://doi.org/10.1007/s11094-020-02172-4

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  • DOI: https://doi.org/10.1007/s11094-020-02172-4

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