Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents

  • A. Karaküçük-İyidoğanEmail author
  • B. Aydınöz
  • T. Taşkın-Tok
  • E. E. Oruç-Emre
  • J. Balzarini

Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC50 = 13 – 27 μg/mL for strain H1N1 and 9.3 – 18 μg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC50 = 0.3 μg/mL for Ig and 1.9 μg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC50 of 0.30, 0.70 and 2.50 μg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies.


aromatic thiosemicarbazone antiviral activity cytostatic activity anti-influenza activity pharmacophore modeling 



The present work was supported by the Scientific Research Projects Governing Unit Council of Gaziantep University (Grant No. FEF.08.10), Gaziantep, Turkey and by the KU Leuven (GOA 10/14). The authors are grateful to Leentje Persoons, Frieda De Meyer, Leen Ingels, Anita Camps, Steven Carmans, Lies Van den Heurck and Lizette van Berckelaer for excellent technical assistance and Dr. Annelies Stevaert for statistical analysis.


  1. 1.
    G. Domagk, R. Behnisch, F. Mietzsch, et al., Naturwissenschaften, 33, 315 (1946).CrossRefGoogle Scholar
  2. 2.
    D. Hamre, J. Bernstein. and R. Donovick, Proc. Soc. Exp. Biol. Med., 73, 275 – 278 (1950).CrossRefGoogle Scholar
  3. 3.
    D. J. Bauer, L. St. Vincent, C. H. Kempe, et al., Lancet, 2, 494 – 496 (1963).CrossRefGoogle Scholar
  4. 4.
    M. A. Soares, J. A., Lessa, I. C. Mendes, et al., Bioorg. Med. Chem., 20, 3396 – 3409. (2012).Google Scholar
  5. 5.
    R. A. Finch, M.-C. Liu, S. P. Grill, et al. Biochem. Pharmacol., 59, 983 – 991 (2000).CrossRefGoogle Scholar
  6. 6.
    V. R. Solomon, C. Hu, and H. Lee, Bioorg. Med. Chem., 18, 1563 – 1572 (2010).CrossRefGoogle Scholar
  7. 7.
    D. M. Noll, T. M. Mason, and P. S. Miller, Chem. Rev., 106, 277 – 301 (2006).CrossRefGoogle Scholar
  8. 8.
    F. F. Fleming, L. Yao, P. C. Ravikumar, et al. J. Med. Chem., 53, 7902 – 7917 (2010).CrossRefGoogle Scholar
  9. 9.
    A. Karaküçük-Iyidoğan, D. Taşdemir, E. E. Oruç-Emre, et al., Eur. J. Med. Chem., 46, 5616 – 5624 (2011).CrossRefGoogle Scholar
  10. 10.
    M. J. Frisch, G. W. Trucks, H. B. Schlegel, et al. Gaussian 09, Revision A.1 Gaussian, Inc., Wallingford CT (2009).Google Scholar
  11. 11.
    Accelrys Software Inc., Discovery Studio 3.5, San Diego (2013).Google Scholar
  12. 12.
    A. Karaküçük-Iyidoğan, Z. Mercan, E. E. Oruç-Emre, et al. Phosphorus Sulfur and Silicon, 189, 661 – 673 (2014).CrossRefGoogle Scholar
  13. 13.
    H. Huang, Q. Chen, X. Ku, et al., J. Med. Chem., 53, 3048 – 3064 (2010).CrossRefGoogle Scholar
  14. 14.
    M. Leigh, D. J. Raines, C.E. Castillo, et al. Chem. Med. Chem., 6, 1107 – 1118 (2011).CrossRefGoogle Scholar
  15. 15.
    A.-C. Tnechiu (Deleanu), I. D. Kostas, D. Kovala-Demertzi, et al. Carbohydr. Res., 344, 1352 – 1364 (2009).Google Scholar
  16. 16.
    V. A. Chornous, A. N. Grozav, L. D. Todoriko, et al. Pharm. Chem. J., 47(10), 524 – 526 (2014).CrossRefGoogle Scholar
  17. 17.
    E. Tsoukala, N. Tzioumaki, S. Manta, et al. Bioorg. Chem., 38, 285 – 293 (2010).CrossRefGoogle Scholar

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

Authors and Affiliations

  • A. Karaküçük-İyidoğan
    • 1
    Email author
  • B. Aydınöz
    • 1
  • T. Taşkın-Tok
    • 1
  • E. E. Oruç-Emre
    • 1
  • J. Balzarini
    • 2
  1. 1.Department of ChemistryGaziantep UniversityGaziantepTurkey
  2. 2.Laboratory of Virology and ChemotherapyRega Institute for Medical Research, KU LeuvenLeuvenBelgium

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