Advertisement

Synthesis of New 6-[4-(2-Fluorophenylpiperazine-1-YL)]-3(2H)-Pyridazinone-2-Acethyl-2- (Substitutedbenzal)Hydrazone Derivatives and Evulation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines

  • Zeynep ÖzdemirEmail author
  • Neşe Başak-Türkmen
  • İdris Ayhan
  • Osman Çiftçi
  • Mehtap Uysal
Article

In this study, seven new 3(2H)-pyridazinone derivatives expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Their structures were confirmed by the IR, 1H-NMR, 13C-NMR spectra and elementary analyses. Compunds V1-V7 were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium] proliferation assay. Human fibroblast cells were used as safety control in these tests. 6-[4-(2-Fluorophenyl)piperazine-1-yl]-3(2H)-pyridazinone-2-acetyl-2-(2-chlorobenzal)hydrazone (compound V3 ) was the most active agent with respect to HEP3B and HTC116 cell lines.

Keywords

pyridazinone cytotoxicity liver cancer colon cancer 

Abbreviations

HEP3B

liver cancer cell line

HTC116

colon cancer cell line

MTS

[3-(4,5-dimethylthi-azol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium]

IC50

half maximum inhibitory concentration

HF

human fibroblast cell line

SHSY5Y

neuroblastoma cell line

TLC

thin layer chromatography

ATR

attenuated total reflection

MM

molecular mass

MP

melting point

Notes

Conflict of Interests

No conflict of interests was reported by all authors.

References

  1. 1.
    J. Ferlay, I. Soerjomataram, R. Dikshit, et al., Int. J. Cancer, 136(5), 359–386 (2015).CrossRefGoogle Scholar
  2. 2.
    N. Howlader, A. M. Noone, M. Krapcho, et al. (eds.), SEER Cancer Statistics Review 1975 – 2014, National Cancer Institute, Bethesda, MD (2017); https: // seer.cancer.gov/csr /1975 2014/.Google Scholar
  3. 3.
    R. Khoogar, B. C. Kim, J. Morris, and M. J. Wargovich, Am. J. Physiol. Gastrointest. Liver Physiol, 310(9), 629 – 644 (2016).CrossRefGoogle Scholar
  4. 4.
    S. M. S. Islam, T. D. Purnat, N. T. A. Phuong, et al., Globalization and Public Health Symp. (March 22, 2014, Munich, Germany) 10:81.Google Scholar
  5. 5.
    F. A. Sloan and H. Gelband, Cancer Control Opportunities in Low- and Middle-Income Countries, National Academies Press, Washington, DC (2007).Google Scholar
  6. 6.
    X. Ma and H. Yu, Yale J. Biol. Med., 79(3 – 4), 85–94 (2006).Google Scholar
  7. 7.
    A. G. Vaiopoulos, I. D. Kostakis, M. Koutsilieris, and A. G. Papavassiliou, Stem Cells, 30(3), 63–371 (2012).CrossRefGoogle Scholar
  8. 8.
    K. Bardhan and K. Liu, Cancer, 5(2), 676–713 (2013).CrossRefGoogle Scholar
  9. 9.
    R. N. Castle, A. Weissberger, and E. C. Taylor, The Chemistry of Heterocyclic Compounds, Vol. 28, John Wiley and Sons, New York (1973).Google Scholar
  10. 10.
    E. Matrai, J. Mol. Struct., 408/409, 467 – 472 (1997).Google Scholar
  11. 11.
    A. R. Katritzky and A. J. Boulton, Advances in Heterocyclic Chemistry, Vol. 9, Academic Press, New York – London (1968).Google Scholar
  12. 12.
    A. A. Siddiqui, R. Mishra, and M. Shaharyar, Eur. J. Med. Chem., 45, 2283 – 2290 (2010).CrossRefGoogle Scholar
  13. 13.
    A. A. Siddiqui, R. Mishra, M. Shaharyar, et al, Bioorg. Med. Chem. Lett., 21, 1023 – 1026 (2011).CrossRefGoogle Scholar
  14. 14.
    S. Utku, M. Gökçe, G. Aslan, et al., Arzneim Forsch, 61, 1 – 7 (92011).Google Scholar
  15. 15.
    C. Yamali, G. H. Ozan, B. Kahya, et al., Med. Chem. Res., 24, 1210 – 1217 (2015). Google Scholar
  16. 16.
    P. Nagle, Y. Pawar, A. Sonawane, et al., Med. Chem. Res., 23, 918 – 926 (2014).Google Scholar
  17. 17.
    M. F. Þahin, B. Badýçoðlu, M. Gökçe, et al., Arch. Pharm. Pharm. Med., 33, 445 – 452 (2004).Google Scholar
  18. 18.
    I. G. Rathish, K. Javed, S. Ahmad, et al., Eur. J. Med. Chem., 49, 304 – 309 (2012).CrossRefGoogle Scholar
  19. 19.
    N. F. Abd El-Ghaffar, M. K. Mohamed, M. S. Kadah, J. Chem. Pharm. Res., 3, 248 – 259 (2011).Google Scholar
  20. 20.
    M. Asif, Int. J. Adv. Chem., 2(2), 148 – 161 (2014).CrossRefGoogle Scholar
  21. 21.
    A. Bruel, C. Loge, M. L. Tauzia, et al., Eur. J. Med. Chem., 57, 225 – 233 (2012).CrossRefGoogle Scholar
  22. 22.
    Z. Özdemir,M. Gökçe, H. Uslu., et al., Intern. Multidisciplinary Symp. on Drug Research and Development (November 28 – 30, 2013, Antalya, Turkey).Google Scholar
  23. 23.
    O. Çiftçi, Z. Özdemir, C. Acar, et al., Lett. Org. Chem., 15(4), 323 – 331 (2017).CrossRefGoogle Scholar
  24. 24.
    T. Önkol, M. Gökçe, İ. Orhan, and F. Kaynak, Org. Commun., 6, 55 – 67 (2013).Google Scholar
  25. 25.
    A. B. Özçelik, M. Gökçe, İ. Orhan, et al., Arzneim Forsch, 60(7), 452 – 458 (2010).Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zeynep Özdemir
    • 1
    Email author
  • Neşe Başak-Türkmen
    • 2
  • İdris Ayhan
    • 3
  • Osman Çiftçi
    • 4
  • Mehtap Uysal
    • 5
  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyInonu UniversityMalatyaTurkey
  2. 2.Department of Pharmaceutical Toxicology, Faculty of PharmacyInonu UniversityMalatyaTurkey
  3. 3.Department of Medical Pharmacology, Faculty of MedicineYıldırım Beyazıt UniversityAnkaraTurkey
  4. 4.Department of Medical Pharmacology, Faculty of MedicinePamukkale UniversityDenizliTurkey
  5. 5.Department of Pharmaceutical Chemistry, Faculty of PharmacyGazi UniversityAnkaraTurkey

Personalised recommendations