Research on Chemical Intermediates

, Volume 41, Issue 9, pp 6575–6587 | Cite as

Synthesis and cytotoxic studies of some novel compounds containing 3-(1H-indol-3-yl)-1H-pyrazole molecular scaffold

  • Datong Zhang
  • Rongrong Xu
  • Shoudong Guo
  • Yaling Zhu


In our efforts to develop effective treatment agents for cancer, a series of novel compounds based on 3-(1H-indol-3-yl)-1H-pyrazole scaffold and three common pharmacophores, namely thiazolidine, 1,3,4-oxadiazole, and acylpyrazole, were synthesized and evaluated for their cytotoxic activity against four human cancer cell lines. Among compounds 2a2c and 3a3c containing thiazolidine moiety, 2b and 3c showed moderate cytotoxic activity toward Ho-8910. The dramatic enhancement in cytotoxic activity was observed upon the introduction of a 1,3,4-oxadiazole-2-thiol moiety on 3-(1H-indol-3-yl)-1H-pyrazole scaffold. Compound 5a was the most effective against KG-1 with IC50 = 6.09 μM, which was comparable to the reference drug doxorubicin. Compound 5b was potent against HepG-2 (IC50 = 9.39 μM) and Ho-8910 (IC50 = 9.41 μM). Compound 5e exhibited IC50 value of 14.12 μM against A-549 and was more potent than other compounds in this series. Compound 5b induced the highest population of apoptotic cells (28.18 %) among the tested compounds at 10 μM. The results obtained from compounds 5 warrant their further optimization as new leads for developing new anticancer agents.


3-(1H-indol-3-yl)-1H-pyrazole Thiazolidine 1,3,4-Oxadiazole Acylpyrazole Synthesis Cytotoxic activity Apoptosis 



This study was supported by the Self-innovation Project for Universities and Institutes of Jinan City (No. 201202035) and Program for Scientific Research Innovation Team in Colleges and Universities of Shandong Province (No. 21376125).

Supplementary material

11164_2014_1762_MOESM1_ESM.doc (737 kb)
Supplementary material 1 (DOC 737 kb)


  1. 1.
    J. Ahmedin, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, M.J. Thun, Cancer J. Clin. 58, 71–96 (2008)CrossRefGoogle Scholar
  2. 2.
    E.R. Lee, Y.J. Kang, H.Y. Choi, G.H. Kim, B.W. Kim, Y.S. Han, S.Y. Nah, H.D. Paik, S.G. Cho, Biol. Pharm. Bull. 30, 2394–2398 (2007)CrossRefGoogle Scholar
  3. 3.
    W. Kenitzer, S. Jiang, Y. Wang, S. Kasibhatla, C. Crogan-Grundy, M. Bubenik, D. Labrecque, R. Denis et al., Bioorg Med Chem Lett 18, 603–607 (2008)CrossRefGoogle Scholar
  4. 4.
    W.P. Hu, H.S. Yu, Y.R. Chen, Y.M. Tsaibhatla, C.C. Liao, L.S. Chang, J.J. Wang, Bioorg. Med. Chem. 16, 5295–5302 (2008)CrossRefGoogle Scholar
  5. 5.
    R. Cao, X. Guan, B. Shi, Z. Chen, Z. Ren, W. Peng, H. Song, Eur. J. Med. Chem. 45, 2503–2515 (2010)CrossRefGoogle Scholar
  6. 6.
    T.C. Leboho, J.P. Michael, W.A.L. van Otterlo, S.F. van Vuuren, C.B. de Koning, Bioorg. Med. Chem. Lett. 19, 4948–4951 (2009)CrossRefGoogle Scholar
  7. 7.
    S.D.M. Basavarajaiah, B.H.M. Mruthyunjayaswamy, Chem. Pharm. Bull. 57, 557–560 (2009)CrossRefGoogle Scholar
  8. 8.
    S. Suzen, E. Buyukbingol, IL Farmaco. 55, 246–248 (2000)CrossRefGoogle Scholar
  9. 9.
    L. Chou, L. Huang, J. Yang, F. Lee, C. Teng, S. Kuo, Bioorg. Med. Chem. 15, 1732–1740 (2007)CrossRefGoogle Scholar
  10. 10.
    G. Daidone, B. Maggio, D. Raffa, S. Plescia, D. Schillaci, M.V. Raimondi, IL Farmaco. 59, 413–417 (2004)CrossRefGoogle Scholar
  11. 11.
    D. Kaushik, S.A. Khan, G. Chawla, S. Kumar, Eur. J. Med. Chem. 45, 3943–3949 (2010)CrossRefGoogle Scholar
  12. 12.
    Z. Cui, Y. Li, Y. Ling, J. Huang, J. Cui, R. Wang, X. Yang, Eur. J. Med. Chem. 45, 5576–5584 (2010)CrossRefGoogle Scholar
  13. 13.
    J. Li, Y. Zhao, X. Zhao, X. Yuan, P. Gong, Arch. Pharm. Chem. Life Sci. 339, 593–597 (2006)CrossRefGoogle Scholar
  14. 14.
    Y. Xia, Z. Dong, B. Zhao, X. Ge, N. Meng, D. Shin, J. Miao, Bioorg. Med. Chem. 15, 6893–6899 (2007)CrossRefGoogle Scholar
  15. 15.
    Y. Xia, C. Fan, B. Zhao, J. Zhao, D. Shin, J. Miao, Eur. J. Med. Chem. 43, 2347–2353 (2008)CrossRefGoogle Scholar
  16. 16.
    D. Zhang, G. Wang, G. Zhao, W. Xu, L. Huo, Eur. J. Med. Chem. 46, 5867–5868 (2011)Google Scholar
  17. 17.
    C.A.M. Fraga, E.J. Barreiro, Curr. Med. Chem. 13, 167–198 (2006)CrossRefGoogle Scholar
  18. 18.
    L.M. Lima, F.S. Frattani, J.L. dos Santos, H.C. Castro, C.A.M. Fraga, R.B. Zingali, E.J. Barreiro, Eur. J. Med. Chem. 43, 348–356 (2008)CrossRefGoogle Scholar
  19. 19.
    P. Diaz, S.S. Phatak, J. Xu, F. Astruc-Diaz, C.N. Cavasotto, M. Naguib, J. Med. Chem. 52, 433–444 (2009)CrossRefGoogle Scholar
  20. 20.
    B.S. Holla, K.N. Poojary, B.S. Rao, M.K. Shivananda, Eur. J. Med. Chem. 37, 511–517 (2002)CrossRefGoogle Scholar
  21. 21.
    Y.A. Al-Soud, N.A. Al-Masoudi, A.E.S. Ferwanah, Bioorg. Med. Chem. 11, 1701–1708 (2003)CrossRefGoogle Scholar
  22. 22.
    N. Demirbas, S.A. Karaoglu, A. Demirbas, K. Sancak, Eur. J. Med. Chem. 39, 793–804 (2004)CrossRefGoogle Scholar
  23. 23.
    A.S. Aboraia, H.M. Abdel-Rahman, N.M. Mahfouz, M.A. EL-Gendy, Bioorg. Med. Chem. 14, 1236–1246 (2006)CrossRefGoogle Scholar
  24. 24.
    R.S. Harisha, K.M. Hosamani, R.S. Keri, Arch. Pharm. Chem. Life Sci. 342, 412–419 (2009)CrossRefGoogle Scholar
  25. 25.
    V. Mathew, J. Keshavayya, V.P. Vaidya, Eur. J. Med. Chem. 41, 1048–1058 (2006)CrossRefGoogle Scholar
  26. 26.
    B.S. Holla, B. Sorojini, S.B. Rao, P.M. Akberali et al., IL Farmaco 56, 565–570 (2001)CrossRefGoogle Scholar
  27. 27.
    M. Kritsanida, A. Mouroutsw, P. Marakos, N. Pouli et al., IL Farmaco 57, 253–257 (2002)CrossRefGoogle Scholar
  28. 28.
    D. Zhang, G. Wang, C. Tan, W. Xu, Y. Pei, L. Huo, Arch. Pharm. Res. 34, 343–355 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Datong Zhang
    • 1
  • Rongrong Xu
    • 1
  • Shoudong Guo
    • 2
  • Yaling Zhu
    • 1
  1. 1.Shandong Provincial Key Laboratory of Fine Chemicals, School of Chemistry and Pharmaceutical EngineeringQilu University of TechnologyJinanPeople’s Republic of China
  2. 2.Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of AtherosclerosisTaishan Medical UniversityTai’anPeople’s Republic of China

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