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Pharmaceutical Chemistry Journal

, Volume 50, Issue 4, pp 234–238 | Cite as

Synthesis and Cytotoxic Activity of (4-Substituted-benzylidene)-(3-Phenyl-1,2,4-Oxadiazol-5-YL)Methylamines

  • K. Kucukoglu
  • M. Tugrak
  • A. Demirtas
  • H. Sakagami
  • H. I. Gul
Article
  • 177 Downloads

This work was aimed at the synthesis and investigation of the cytotoxic activity of a series of Schiff bases having (4-substituted-benzylidene)-(3-phenyl-1,2,4-oxadiazol-5-yl)methylamine structure with different electronic natures of substituents in the phenyl ring. Thus, the study was intended to observe the effect of substituents with different electronic properties on the cytotoxic activity. The synthesized series of compounds (OP) were obtained by six-step synthesis with yields ranging from 12.23 to 25.77%. The chemical structures of these compounds were elucidated by H NMR. The cytotoxicity of compounds against human oral squamous cell carcinoma cell lines [Ca9-22 (gum), HSC-2 (mouth), HSC-3 (fluent), HSC-4 (language)] and human oral normal cells [HGF (gum fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts)] was tested by MTT assay. Among the group of six OP compounds, bromo derivative OP2, non-substituted derivative OP1, and chloro derivative OP3 showed higher cytotoxicity (2.71-, 1.56-, and 1.53-fold, respectively) than the reference compound 5-FU. In addition, OP2 (3.27) exhibited the greatest selectivity index in this group. These compounds can be considered to be model structures for further studies.

Keywords

1,2,4-oxadiazole Gabriel synthesis Schiff base cytotoxicity 

Notes

Acknowledgments

The authors thank the Scientific and Technological Research Council of Turkey (TUBITAK) for financial support (Project Number: 114S584) and Ataturk University Faculty of Science Department of Organic Chemistry for taking 1H NMR spectra of compounds.

References

  1. 1.
    S. J. Shaw, Mini Rev. Med. Chem., 8 (3), 276 – 284 (2008).CrossRefPubMedGoogle Scholar
  2. 2.
    H. Varmus, Science, 312 (5777), 1162 – 1165 (2006).CrossRefPubMedGoogle Scholar
  3. 3.
    M. R. Harrison, K. D. Holen, and G. Liu, Clin. Adv. Hematol. Oncol., 7 (1), 54 – 64 (2009).PubMedPubMedCentralGoogle Scholar
  4. 4.
    G. D. Diana, D. L. Volkots, T. J. Nitz, et al., J. Med. Chem., 37 (15), 2421 – 2436 (1994).CrossRefPubMedGoogle Scholar
  5. 5.
    R. H. Tale, A. H. Rodge, A. P. Keche, et al., J. Chem. Pharm. Res., 3(2), 496 – 505 (2011).Google Scholar
  6. 6.
    J. W. Watthey, M. Desai, R. Rutledge, et al., J. Med. Chem., 23 (6), 690 – 692 (1980).CrossRefPubMedGoogle Scholar
  7. 7.
    H. J. Lankau, K. Unverferth, C. Grunwald, et al., Eur. J. Med. Chem., 42 (6), 873 – 879 (2007).CrossRefPubMedGoogle Scholar
  8. 8.
    H. Z. Zhang, S. Kasibhatla, J. Kuemmerle, et al., J. Med. Chem., 48 (16), 5215 – 5223 (2005).CrossRefPubMedGoogle Scholar
  9. 9.
    D. Kumar, G. Patel, E. O. Johnson, et al., Bioorg. Med. Chem. Lett., 19 (10), 2739 – 2741 (2009).CrossRefPubMedGoogle Scholar
  10. 10.
    D. Kumar, G. Patel, A. K. Chavers, et al., Eur. J. Med. Chem., 46 (7), 3085 – 3092 (2011).CrossRefPubMedGoogle Scholar
  11. 11.
    J. Cai, H.Wei, K. H. Hong, et al., Eur. J. Med. Chem., 96, 1 – 13 (2015).CrossRefPubMedGoogle Scholar
  12. 12.
    Z. Cimerman, S. Miljanic, and N. Galic, Croat. Chem. Acta, 73 (1), 81 – 95 (2000).Google Scholar
  13. 13.
    P. Vicini, A. Geronikaki, M. Incerti, et al., Bioorg. Med. Chem., 11 (22), 4785 – 4789 (2003).CrossRefPubMedGoogle Scholar
  14. 14.
    M. T. Tarafder, A. Kasbollah, N. Saravanan, et al., J. Biochem. Mol. Biol. Biophys., 6 (2), 85 – 91 (2002).CrossRefPubMedGoogle Scholar
  15. 15.
    L. Shi, H. M. Ge, S. H. Tan, et al., Eur. J. Med. Chem., 42 (4), 558 – 564 (2007).CrossRefPubMedGoogle Scholar
  16. 16.
    K. Cheng, Q. Z. Zheng, J. Hou, et al., Bioorg. Med. Chem., 18 (7), 2447 – 2455 (2010).CrossRefPubMedGoogle Scholar
  17. 17.
    K. Cheng, Q. Z. Zheng, Y. Qian, et al., Bioorg. Med. Chem., 17 (23), 7861 – 7871 (2009).CrossRefPubMedGoogle Scholar
  18. 18.
    I. Kucukguzel, S. Guniz Kucukguzel, S. Rollas, et al., Farmaco, 59 (11), 893 – 901 (2004).CrossRefPubMedGoogle Scholar
  19. 19.
    N. P. Rai, V. K. Narayanaswamy, T. Govender, et al., Eur. J. Med. Chem., 45 (6), 2677 – 2682 (2010).CrossRefPubMedGoogle Scholar
  20. 20.
    H. R. Lawrence, S. Ozcan, and S. M. Sebti, WO2012129564 A2 (2012).Google Scholar
  21. 21.
    A. Q. Hussein, Heterocycles, 26 (1), 163 – 173 (1987).CrossRefGoogle Scholar
  22. 22.
    Q. Zhao, S. Liu, Y. Li, et al., J. Agric. Food Chem., 57 (7), 2849 – 2855 (2009).CrossRefPubMedGoogle Scholar
  23. 23.
    F. Sigmund and R. Uchann, Monatch. Chem., 51, 250 (1929).Google Scholar
  24. 24.
    E. Saripinar, Y. Guzel, Z. Onal, et al., J. Chem. Soc. Pakistan, 22, 308 – 317 (2000).Google Scholar
  25. 25.
    E. Şahin, Author’s Abstract of Cand. Sci. (Chem.) Ms Thesis, Kayseri (2007).Google Scholar
  26. 26.
    S. Bilginer, H. I. Gul, E. Mete, et al., J. Enzyme Inhib. Med. Chem., 28 (5), 974 – 980 (2013).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyAtaturk UniversityErzurumTurkey
  2. 2.Division of Pharmacology, School of DentistryMeikai UniversitySakadoJapan

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