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Design, synthesis, anticancer activity and cytotoxicity of novel 4-piperidone/cyclohexanone derivatives

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Abstract

Design and synthesis of two series of novel double Schiff-base substituted 4-piperidone/cyclohexanone derivatives, like curcumin analogues, series 1 (1a–d) and 2 (2a–e) were generated and characterized by 1H NMR, 13C NMR, IR, and elemental analysis. The anticancer activities against human carcinoma cell lines HePG2, HeLa, K562, THP-1, and their cytotoxicities for LO2 cell lines were subsequently evaluated by the MTT method. The results show that series 2 (2a–e) have the better anticancer activity than series 1 (1a–d) in spite of the bigger cytotoxicity of series 2. Structure analysis shows that the N-methyl-4-piperidinone group and the introduction of hydroxy is helpful for improving their anticancer activity, especially 2a, 2d and 2e, and their IC50 values against THP-1 cells can reach 0.69–0.96 μM.

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References

  1. A. Goel, A.B. Kunnumakkara, B.B. Aggarwal, Biochem. Pharmacol. 75, 787 (2008)

    Article  CAS  Google Scholar 

  2. C.R.A. Souza, S.F. Osme, M.B.A. Glória, J. Food Process Preserv. 21, 353 (1997)

    Article  CAS  Google Scholar 

  3. B.B. Aggarwal, C. Sundaram, C.A. Mosley, D.C. Liotta, V.P. Menon, A.R. Sudheer, S. Shishodia, T. Singh, Y.J. Surh, K.S. Chun, Adv. Exp. Med. Biol. 595, 425 (2007)

    Article  Google Scholar 

  4. F.W. Daube, Ber. Dtsch. Chem. Ges. 3, 609 (1870)

    Article  Google Scholar 

  5. H.P. Ammon, M.A. Wahl, Planta Med. 57, 1 (1991)

    Article  CAS  Google Scholar 

  6. C.J. Li, L.J. Zhang, B.J. Dezube, C.S. Crumpacker, A.B. Pardee, Proc. Natl. Acad. Sci. 90, 1839 (1993)

    Article  CAS  Google Scholar 

  7. N. Kandaswamy, N. Raveendiran, Res. Chem. Intermed. 41, 7189 (2014)

    Article  Google Scholar 

  8. J.H. Naama, G.H. Alwan, H.R. Obayes, A.A. Al-Amiery, A.A. Al-Temimi, A.A.H. Kadhum, A.B. Mohamad, Res. Chem. Intermed. 39, 4047 (2013)

    Article  CAS  Google Scholar 

  9. R. Motterlini, R. Foresti, R. Bassi, C.J. Green, Free Radic. Biol. Med. 28, 1303 (2000)

    Article  CAS  Google Scholar 

  10. A. Prathapan, M. Lukhman, C. Arumughan, A. Sundaresan, K.G. Raghu, Int. J. Food Sci. Technol. 44, 1438 (2009)

    Article  CAS  Google Scholar 

  11. D. Umashankar, A. Jane, S. Anuraag, R.K. Sharma, D.C. Erik, B. Jan, J.R. Dimmock, Eur. J. Med. Chem. 42, 71 (2007)

    Article  Google Scholar 

  12. P. Anand, S.A. Thomas, C. Sundaram, K. Harikumar, B. Sung, S. Tharakan, K. Misra, I. Priyadarsin, K. Rajasekharan, B. Aggarwal, Biochem. Pharmacol. 76, 1590 (2008)

    Article  CAS  Google Scholar 

  13. L.J. Zhang, C.F. Wu, X.L. Meng, D. Yuan, X.D. Cai, Q.L. Wang, J.Y. Yang, Neurosci. Lett. 447, 48 (2008)

    Article  CAS  Google Scholar 

  14. S. Das, U. Das, D. Michel, D.K.J. Gorecki, J.R. Dimmock, Eur. J. Med. Chem. 64, 321 (2013)

    Article  CAS  Google Scholar 

  15. A.D. Kumar, M.P. Kumar, Med. Res. Rev. 30, 818 (2010)

    Google Scholar 

  16. Y. Santiago-Vazquez, S. Das, U. Das, E. Robles-Escajeda, N.M. Ortega, C. Lema, A. Varela-Ramírez, R.J. Aguilera, J. Balzarini, E. De Clercq, Eur. J. Med. Chem. 77, 315 (2014)

    Article  CAS  Google Scholar 

  17. S. Das, U. Das, H. Sakagami, N. Umemura, S. Iwamoto, T. Matsuta, M. Kawase, J. Molnár, J. Serly, D.K.J. Gorecki, Eur. J. Med. Chem. 51, 193 (2012)

    Article  CAS  Google Scholar 

  18. P. Lagisetty, P. Lagisetty, K. Sahoo, S. Anant, V. Awasthi, Bioorg. Med. Chem. 18, 6109 (2010)

    Article  CAS  Google Scholar 

  19. J.F. Sun, S.P. Zhang, C. Yu, G.G. Hou, X.F. Zhang, K.K. Li, F. Zhao, Chem. Biol. Drug Des. 83, 392 (2013)

    Article  Google Scholar 

  20. U. Das, H. Sakagami, Q. Chu, Q. Wang, M. Kawase, P. Selvakumar, R.K. Sharma, J.R. Dimmock, Bioorg. Med. Chem. 20, 912 (2010)

    Article  CAS  Google Scholar 

  21. I. Huber, I. Zupkó, I.J. Kovács, R. Minorics, G. Gulyás-Fekete, G. Maász, P. Perjési, Monatshefte für Chemie - Chemical Monthly 146, 973 (2015)

    Article  CAS  Google Scholar 

  22. B.K. Adams, E.M. Ferstl, M.C. Davis, M. Herold, S. Kurtkaya, R.F. Camalier, M.G. Hollingshead, G. Kaur, E.A. Sausville, F.R. Rickles, J.P. Snyder, D.C. Liotta, M. Shoji, Bioorg. Med. Chem. 12, 3871 (2004)

    Article  CAS  Google Scholar 

  23. P. Lagisetty, P. Vilekar, K. Sahoo, S. Anant, V. Awasthi, Bioorg. Med. Chem. 18, 6109 (2010)

    Article  CAS  Google Scholar 

  24. J.F. Sun, S.P. Zhang, C. Yu, G.G. Hou, X.F. Zhang, K.K. Li, F. Zhao, Chem. Biol. Drug Des. 83, 392 (2014)

    Article  CAS  Google Scholar 

  25. W.S. Liu, Q. Chen, J.F. Sun, C.H. Wang, F. Zhao, G.G. Hou, J. Instrum. Anal. 34, 900 (2015)

    CAS  Google Scholar 

  26. W.S. Liu, J.F. Sun, C.H. Wang, G.G. Hou, Chem. Reag. 37, 885 (2015)

    CAS  Google Scholar 

  27. H.J. Li, L. Wang, J.J. Zhao, J.F. Sun, J.L. Sun, C.H. Wang, G.G. Hou, J. Mol. Struct. 1079, 414 (2015)

    Article  CAS  Google Scholar 

  28. L.D. Liu, S.L. Liu, Z.X. Liu, G.G. Hou, J. Mol. Struct. 1112, 1 (2016)

    Article  CAS  Google Scholar 

  29. C.M. Da Silva, D.L. Da Silva, L.V. Modolo, R.B. Alves, M.A. De Resende, C.V.B. Martins, A. de Fatima, J. Adv. Res. 2, 1 (2011)

    Article  Google Scholar 

  30. P. Przybylski, A. Huczynski, K. Pyta, B. Brzezinski, F. Bartl, Curr. Org. Chem. 13, 124 (2009)

    Article  CAS  Google Scholar 

  31. J.A. Makawana, C.B. Sangani, L. Lin, H.L. Zhu, Bioorg. Med. Chem. Lett. 24, 1734 (2014)

    Article  CAS  Google Scholar 

  32. J. Azizian, M.K. Mohammadi, O. Firuzi, N. Razzaghi-Asl, R. Miri, Med. Chem. Res. 21, 3730 (2012)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful for financial support from the National Natural Science Foundation of China (No. 21402010), the Foundation of Shandong province (Nos. ZR2013BM022, ZR2014HP006, ZR2014BL008, 2014CGZH1316, 2015GGX102013), and the Foundation of Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals (No. ZDSYS-KF201505).

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    Authors and Affiliations

    1. The Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, China

      Qin Chen, Yun Hou, Gui-Ge Hou, Ju-Feng Sun, Ning Li, Wei Cong, Feng Zhao, Hong Juan Li & Chun-Hua Wang

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    1. Qin Chen
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    2. Yun Hou
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    Correspondence to Gui-Ge Hou or Chun-Hua Wang.

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    Qin Chen and Yun Hou have contributed equally to this work.

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    Chen, Q., Hou, Y., Hou, GG. et al. Design, synthesis, anticancer activity and cytotoxicity of novel 4-piperidone/cyclohexanone derivatives. Res Chem Intermed 42, 8119–8130 (2016). https://doi.org/10.1007/s11164-016-2583-y

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