Skip to main content
SpringerLink
Log in

Green synthesis and evaluation of the antitumor activity of a novel series of 3-[4-bi-(4-fluorophenyl)methylpiperazinyl]-4-amino-5-thione-1,2,4-triazole Schiff bases

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

Fourteen novel 1,2,4-triazole Schiff bases containing the 1-[bi-(4-fluorophenyl)methyl]piperazine group were prepared, in good yield (73–85 %), in five steps starting from 1-[bi-(4-fluorophenyl)methyl]piperazine and ethyl chloroacetate, with use of microwave irradiation. The structures of the new compounds were characterized by IR spectroscopy, MS, 1H and 13C NMR spectroscopy, and elemental analysis. Assay of the newly prepared compounds for bioactivity against tumor cells revealed that the most of the compounds had good to excellent inhibitory activity against CDC25B (99.70 % inhibition). The 4-amino-5-[4-bi-(4-fluorophenyl) methylpiperazin-1-ylmethyl]-1,2,4-triazole-3-thione group was found to be beneficial group improving anti-tumor activity to some extent.

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

Similar content being viewed by others

References

  1. V. Sumangala, B. Poojary, N. Chidananda, T. Arulmoli, S. Shenoy, Facile synthesis, cytotoxic and antimicrobial activity studies of a new group of 6-aryl-3-[4-(methyl-sulfonyl)benzyl]-7H-[1, 2, 4]triazolo[3,4-b][1, 3, 4]thiadiazines. Eur J Med Chem 54, 59–64 (2012)

    Article  CAS  Google Scholar 

  2. B.F. Abdel-Wahab, E. Abdel-Latif, H.A. Mohamed, G.E.A. Awad, Design and synthesis of new 4-pyrazolin-3-yl-1,2,3-triazoles and 1,2,3-triazol-4-yl-pyrazolin -1-yl thiazoles as potential antimicrobial agents. Eur J Med Chem 52, 263–268 (2012)

    Article  CAS  Google Scholar 

  3. S.A. Almasirad, M. Tabatabai, A. Faizi, N. Kebriaeezadeh, A. Mehrabi, A.S. Dalvandi, Synthesis and anti-convulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem Lett 14, 6057–6059 (2004)

    Article  CAS  Google Scholar 

  4. A.T. Mavrova, D. Wesselinova, Y.A. Tsenov, P. Denkova, Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells. Eur J Med Chem 44, 63–69 (2009)

    Article  CAS  Google Scholar 

  5. S. Adsule, V. Barve, D. Chen, F. Ahmed, Q.P. Dou, S. Padhye, F.H. Sarkar, Novel schiff base copper complexes of quinoline-2-carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J Med Chem 49, 7242–7246 (2006)

    Article  CAS  Google Scholar 

  6. N.H. Khan, N. Pandya, N.C. Maity, M. Kumar, R.M. Patel, R.I. Kureshy, S.H.R. Abdi, S. Mishra, S. Das, H.C. Bajaj, Influence of chirality of V(V) Schiff base complexes on DNA, BSA binding and cleavage activity. Eur J Med Chem 46, 5074–5085 (2011)

    Article  CAS  Google Scholar 

  7. G. Kumar, S. Devi, R. Johari, D. Kumar, Synthesis, spectral characterization and antimicrobial evaluation of Schiff base Cr(III), Mn(III) and Fe(III) macrocyclic complexes. Eur J Med Chem 52, 269–274 (2012)

    Article  Google Scholar 

  8. H. Bayrak, A. Demirbas, S.A. Karaoglu, N. Demirbas, Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities. Eur J Med Chem 44, 1057–1066 (2009)

    Article  CAS  Google Scholar 

  9. A.M. Isloor, B. Kalluraya, P. Shetty, Regioselective reaction: synthesis, characterization and pharmacological studies of some new Mannich bases derived from 1,2,4-triazoles. Eur J Med Chem 44, 3784–3787 (2009)

    Article  CAS  Google Scholar 

  10. Nithinchandra, B. Kalluraya, S. Aamir, A.R. Shabaraya, Regioselective reaction: synthesis, characterization and pharmacological activity of some new Mannich and Schiff bases containing sydnone. Eur J Med Chem 54, 597–604 (2012)

    Article  CAS  Google Scholar 

  11. B. Soni, M.S. Ranawat, R. Sharma, A. Bhandari, S. Sharma, Synthesis and evaluation of some new benzothiazole derivatives as potential antimicrobial agents. Eur J Med Chem 45, 2938–2942 (2010)

    Article  CAS  Google Scholar 

  12. Y.L. Peng, X.L. Liu, J. Gu, Z.G. Zhao, Microwave-assisted synthesis and antibacterial activity of methyl 1-{2-[4-amino-5-(naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio]ethyl}-1H-indole-3-carboxylate derivatives. J Chem Res 37, 413–416 (2013)

    Article  CAS  Google Scholar 

  13. X.H. Sun, Y. Tao, Y.F. Liu, B. Chen, Y.Q. Jia, J.W. Yang, Synthesis and biological activities of alkyl substituted triazolethione Schiff base. Chin J Chem 26, 1133–1136 (2008)

    Article  CAS  Google Scholar 

  14. G.Q. Hu, L.L. Hou, S.Q. Xie, W.L. Huang, Design, synthesis and antitumor activity of asymmetric bis(s-triazole Schiff base)s Bearing functionalized side-chain. Chin J Chem 26, 1145–1149 (2008)

    Article  CAS  Google Scholar 

  15. X.J. Yang, J.T. Liu, F.L. Zhao, Reactions of 2,2-dihydropolyfluoroalkyl- aldehydes with amines: a facile synthetic method for fluoroalkyl enaminoketones. J Fluorine Chem 125, 415–419 (2004)

    Article  CAS  Google Scholar 

  16. S. Yoshida, O.G.J. Meyer, T.C. Rosen, G. Haufe, Y. Song, M.J. Sloan, K.L. Kirk, Fluorinated phenylcyclo-propylamines. 1. Synthesis and effect of fluorine substitution at the cyclopropane ring on inhibition of microbial tyramine oxidase. J Med Chem 47, 1796–1806 (2004)

    Article  CAS  Google Scholar 

  17. S.N. Shelke, G.R. Mhaske, V.D.B. Bonifàcio, M.B. Gawande, Green synthesis and anti-infective activities of fluorinated pyrazoline derivatives. Bioorg Med Chem Lett 22, 5727–5730 (2012)

    Article  CAS  Google Scholar 

  18. Q.H. Li, Y. Ding, N.W. Huang, Synthesis and biological activities of dithiocarbamates containing 1,2,3-triazoles group. Chin Chem Lett 25, 1469–1472 (2014)

    Article  CAS  Google Scholar 

  19. Z.M. Ge, B.G. Guo, H.Y. Wang, T.M. Cheng, R.T. Li, Synthesis and antitumor activity of 1-[4-bi-(4-fluorophenyl)-methyl]-4-substituted piperazines. J. Peking Univ. (Heal. Sci.) 33, 213–216 (2001). (in Chinese)

    CAS  Google Scholar 

  20. A. Dhainaut, G. Regnier, A. Tizot, A. Pierre, S. Leonce, N. Guilbaud, L. Kraus-Berthier, G. Atassi, New purines and purine analogs as modulators of multidrug resistance. J Med Chem 39, 4099–4108 (1996)

    Article  CAS  Google Scholar 

  21. R.T. Li, S.L. Cao, H.C. Chen, J.Z. Yang, M.S. Cai, Synthesis and pharmacological activities of 1,1-dialkyl-4-(3-bromopropionyl)piperazinium bromides. Acta Pharm Sin 31, 757–760 (1996)

    CAS  Google Scholar 

  22. N. Sugiyama, F. Akahoshi, S. Kuwahara, M. Kajii, Y. Sakaue, H. Yakumaru, M. Sugiura, C. Fukaya, Synthesis and topical anti-inflammatory and antiallergic activities of antioxidant o-aminophenol derivatives. J Med Chem 37, 1977–1982 (1994)

    Article  CAS  Google Scholar 

  23. X.C. Liao, C.L. Rong, X.L. Wu, J.C. Zhang, Y.Z. Yu, Y.F. Zhao, Synthesis of 1-difluorobenzene-4-acylpiperazines derivatives. Chem. Res. Appl. 16, 496–498 (2004). (in Chinese)

    CAS  Google Scholar 

  24. B.A. Roberts, C.R. Strauss, Toward rapid, “Green”, predictable microwave-assisted synthesis. Acc Chem Res 38, 653–661 (2005)

    Article  CAS  Google Scholar 

  25. V. Polshettiwar, R.S. Varma, Greener and rapid access to bioactive heterocycles: one-pot solvent-free synthesis of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles. Tetrahedron Lett 49, 879–883 (2008)

    Article  CAS  Google Scholar 

  26. B.T. Zeng, Z.G. Zhao, L.J. Zhou, Q.H. Li, Synthesis of novel chiral cholic acid-based molecular tweezers containing unsymmetrically disubstituted urea units using microwave irradiation. J Chem Res 36, 206–209 (2012)

    Article  CAS  Google Scholar 

  27. Q.H. Li, Z.G. Zhao, Microwave-assisted synthesis of new N 4-[bi-(4-fluoro -phenyl)methyl]piperazine thiosemicarbazones under solvent-free conditions. Chin Chem Lett 19, 1035–1038 (2008)

    Article  CAS  Google Scholar 

  28. Q.H. Li, Z.G. Zhao, Microwave-assisted synthesis of 2-[4-bi-(4-fluorophenyl)-methylpiperazin-1-yl]Acteyl Hydrazones. Chin. J. Org. Chem. 29, 119–122 (2009). (in Chinese)

    Google Scholar 

  29. H.W. Wang, W.J. Zhu, Z.R. Yu, J. Li, B.D. Dong, X.C. Liao, Synthesis and structure characterization of sulfur ethers containing 1,2,4-triazole and 1,3,4-oxadiazole. Chin. J. Org. Chem. 32, 1888–1893 (2012). (in Chinese)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the National Center for Drug Screening, Shanghai, P.R. China, for evaluation of inhibitory activity against CDC25B. We also thank the Fundamental Research Funds for the Central Universities, Southwest University for Nationalities (no. 12NZYTH03), the Sichuan Provincial Department of science and technology support program (no. 2015NZ0033), and the Postgraduate Degree Construction Project of Southwest University for Nationalities (no. 2014XWD-S0703) for financial support.

Author information

Authors and Affiliations

  1. College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu, 610041, China

    Yong Ding, Zhen Zhang, Gang Zhang, Song Mo, Qinghan Li & Zhigang Zhao

Authors
  1. Yong Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Song Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qinghan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhigang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qinghan Li.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, Y., Zhang, Z., Zhang, G. et al. Green synthesis and evaluation of the antitumor activity of a novel series of 3-[4-bi-(4-fluorophenyl)methylpiperazinyl]-4-amino-5-thione-1,2,4-triazole Schiff bases. Res Chem Intermed 42, 3105–3116 (2016). https://doi.org/10.1007/s11164-015-2200-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-015-2200-5

Keywords

Search

Navigation