Research on Chemical Intermediates

, Volume 44, Issue 9, pp 5635–5652 | Cite as

Design, synthesis and spectroscopic and crystallographic characterisation of novel functionalized pyrazole derivatives: biological evaluation for their cytotoxic, angiogenic and antioxidant activities

  • Achutha Dileep Kumar
  • Srinivasan Bharath
  • Rekha N. Dharmappa
  • Shivalingegowda Naveen
  • Neratur Krishnappagowda Lokanath
  • Kariyappa Ajay KumarEmail author


The current study presents the synthesis of functionalized pyrazoles (18–29) through 3 + 2 annulation reaction of ethyl 2-(arylidene)-3-oxobutanoates (8–13) with phenylhydrazine hydrochlorides (14–17) in acetic acid under reflux conditions. Structures of the synthesized new compounds were characterized by spectral and single-crystal X-ray diffraction studies. Preliminary assessment on their biological activities showed that compounds 19, 23 and 28 have anticancer and antiangiogenic properties and compounds 20, 24 and 26 have excellent diphenylpicrylhydrazyl (DPPH) radical scavenging activities. Detailed quantitative structure–activity relationship (QSAR) analysis provided insights into the molecular features that might have contributed towards increasing potency of inhibition. In summary, we present a study that has successfully demonstrated the synthesis of novel pyrazole analogues that display anticancer, antiangiogenic and DPPH free radical scavenging activities, making them lead molecules of choice for further development.

Graphical Abstract


Antiangiogenic Antioxidant Citotoxic Condensation Pyrazoles 



The authors are grateful to the IOE Instrumentation Facility, Vijnana Bhavana, University of Mysore, for recording spectra and X-ray diffraction studies, and JSS College of Pharmacy, Mysuru, for providing cell lines.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest including financial, personal or other relationships with other people or organizations for this article.


  1. 1.
    S. Eckhardt, Curr. Med. Chem. 3, 419 (2002)Google Scholar
  2. 2.
    R. Katoch-Rouse, O.A. Pavlova, T. Caulder, A.F. Hoffmann, A.G. Mukhin, A.G. Horti, J. Med. Chem. 46, 642 (2003)CrossRefPubMedGoogle Scholar
  3. 3.
    O. Bruno, F. Bondavalli, A. Ranise, P. Schenone, C. Losasso, L. Cilenti, C. Matera, E. Marmo, Farmaco 45, 147 (1990)PubMedGoogle Scholar
  4. 4.
    D.M. Lokeshwari, D.K. Achutha, B. Srinivasan, N. Shivalingegowda, L.N. Krishnappagowda, A.K. Kariyappa, Bioorg. Med. Chem. Lett. 27, 3806 (2017)CrossRefPubMedGoogle Scholar
  5. 5.
    Z. Sui, J. Guan, M.P. Ferro, K. McCoy, M.P. Wachter, W.V. Murray, M. Singer, M. Steber, D.M. Ritchie, D.C. Argentieri, Bioorg. Med. Chem. Lett. 10, 601 (2000)CrossRefPubMedGoogle Scholar
  6. 6.
    J.S. Pasin, A.P. Ferreira, A.L. Saraiva, V. Ratzlaff, R. Andrighetto, P. Machado, S. Marchesan, R.A. Zanette, H.G. Bonacorso, N. Zanatta, M.A. Maritins, J. Ferreira, C.F. Mello, Braz. J. Med. Biol. Res. 43, 1193 (2010)CrossRefPubMedGoogle Scholar
  7. 7.
    S.R. Stauffer, C.J. Coletta, R. Tedesco, G. Nishiguchi, K. Carlson, J. Sun, B.S. Katzenellenbogen, J.A. Katzenellenbogen, J. Med. Chem. 43, 4934 (2000)CrossRefPubMedGoogle Scholar
  8. 8.
    M.J. Ahsan, Arab. J. Chem. 10, S2762 (2017)CrossRefGoogle Scholar
  9. 9.
    D. Secci, A. Bolasco, P. Chimenti, S. Carradori, Curr. Med. Chem. 18, 5114 (2011)CrossRefPubMedGoogle Scholar
  10. 10.
    A.D. Prasanna, R.J. Sonali, Int. J. Med. Chem. 2015, 670181 (2015)Google Scholar
  11. 11.
    L.D. Mahadevaswamy, A.K. Kariyappa, Pharm. Chem. J. 51, 670 (2017)CrossRefGoogle Scholar
  12. 12.
    C. Lamberth, Heterocycles 71, 1467 (2007)CrossRefGoogle Scholar
  13. 13.
    J. Prabhashankar, V.K. Govindappa, A.K. Kariyappa, Turk. J. Chem. 37, 853 (2013)CrossRefGoogle Scholar
  14. 14.
    K. Mohanan, A.R. Martin, L. Toupet, M. Smietana, J.-J. Vasseur, Angew. Chem. Int. Ed. 49, 3196 (2010)CrossRefGoogle Scholar
  15. 15.
    O.K. Yang, Y.S. Chun, C.-L. Park, Y. Kim, H. Shin, S. Ahn, J. Hong, S. Lee, Org. Biomol. Chem. 7, 1132 (2009)CrossRefGoogle Scholar
  16. 16.
    P. Jayaroopa, K. Ajay Kumar, Int. J. Pharm. Pharm. Sci. 5(4), 431 (2013)Google Scholar
  17. 17.
    A.R. Katrizky, M. Wang, S. Zhang, M.V. Voronkov, J. Org. Chem. 66, 6787 (2001)CrossRefGoogle Scholar
  18. 18.
    D. Ribatti, A. Vacca, L. Roncali, F. Dammacco, Haematologica 76, 311 (1991)PubMedGoogle Scholar
  19. 19.
    R. Domenico, V. Angelo, R. Luisa, D. Franco, Curr. Pharm. Biotechnol. 1, 73 (2000)CrossRefGoogle Scholar
  20. 20.
    M.E. Buyukokuroglu, I. Gulcin, M. Oktay, O.I. Kufrevioglu, Pharmacol. Res. 44, 491 (2001)CrossRefPubMedGoogle Scholar
  21. 21.
    A.I. Ismiyev, Acta Crystallogr. Sect. E Struct. Rep Online E67, o1863 (2011)CrossRefGoogle Scholar
  22. 22.
    A.K. Kariyappa, N. Shivalingegowda, D.K. Achutha, N.K. Lokanath, Chem. Data Collect. 3–4, 1 (2016)CrossRefGoogle Scholar
  23. 23.
    A. Dileep Kumar, S. Naveen, H.K. Vivek, M. Prabhuswamy, N.K. Lokanath, K. Ajay Kumar, Chem. Data Collect. 5–6, 36 (2016)CrossRefGoogle Scholar
  24. 24.
    A. Dileep Kumar, K. Kumara, N.K. Lokanath, K. Ajay Kumar, M. Prabhuswamy, Chem. Data Collect. 5–6, 68 (2016)Google Scholar
  25. 25.
    S. Hong, Y. Shin, M. Jung, M.W. Ha, Y. Park, Y.-J. Lee, J. Shin, K.B. Oh, S.K. Lee, H.-G. Park, Eur. J. Med. Chem. 96, 218 (2015)CrossRefPubMedGoogle Scholar
  26. 26.
    W.H. Correa, J.L. Scott, Green Chem. 3, 296 (2001)CrossRefGoogle Scholar
  27. 27.
    Chandra, N. Srikantamurthy, E.A. Jithesh Babu, K.B. Umesha, M. Mahendra, AIP Conf. Proc. 1591, 1197 (2014)CrossRefGoogle Scholar
  28. 28.
    S. Naveen, A. Dileep Kumar, K. Kumara, K. Ajay Kumar, N.K. Lokanath, I. Warad, IUCrData 1, x161972 (2016)CrossRefGoogle Scholar
  29. 29.
    S.C. Michael, L. Sandra, M.K. Konstantinos, A.H. Serkos, Bioorg. Med. Chem. 18, 4338 (2010)CrossRefGoogle Scholar
  30. 30.
    V.L. Ranganatha, F. Zameer, S. Meghashri, N.D. Rekha, V. Girish, H.D. Gurupadaswamy, S.A. Khanum, Arch. Pharm. Chem. Life Sci. 346, 901 (2013)CrossRefGoogle Scholar
  31. 31.
    M.S. Blois, Nature 181, 1199 (1958)CrossRefGoogle Scholar
  32. 32.
    N. Renuka, H.K. Vivek, G. Pavithra, K. Ajay Kumar, Russ. J. Bioorg. Chem. 43, 197 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Achutha Dileep Kumar
    • 1
  • Srinivasan Bharath
    • 2
  • Rekha N. Dharmappa
    • 3
  • Shivalingegowda Naveen
    • 4
  • Neratur Krishnappagowda Lokanath
    • 5
  • Kariyappa Ajay Kumar
    • 1
    Email author
  1. 1.Department of Chemistry, Yuvaraja’s CollegeUniversity of MysoreMysuruIndia
  2. 2.Marie Skłodowska-Curie ActionsOeirasPortugal
  3. 3.Department of BiotechnologyJSS College for Arts, Commerce and ScienceMysuruIndia
  4. 4.Department of Physics, School of Engineering and TechnologyJain UniversityBangaloreIndia
  5. 5.Department of Studies in PhysicsManasagangotri, University of MysoreMysuruIndia

Personalised recommendations