Skip to main content

Advertisement

SpringerLink
Log in

Anti-cancer, anti-oxidant and molecular docking studies of thiosemicarbazone indole-based derivatives

  • Published:
Research on Chemical Intermediates Aims and scope Submit manuscript

Abstract

Based on the structural elements of bioactive 3-substituted indoles, a new series of indole–thiosemicarbazone hybrid derivatives were designed, synthesized, and well-characterized using different spectral techniques. The intended scaffolds were screened for their in vitro anti-proliferative activities against breast cancer (MCF-7), lung cancer (A-549), and liver cancer (Hep-G2) cell lines, as well as their anti-oxidant properties. Cytotoxicity studies revealed that compound 6n was the most potent, at least threefold more potent than the commercially available reference drug etoposide, against A-549. In addition, morphological analysis by the acridine orange/ethidium bromide double staining test and flow cytometry analysis confirmed induction of apoptosis in the A-549 cells by compound 6n. In order to validate the experimental results, molecular studies were performed to achieve the possible binding interactions of the most potent compound (6n) and colchicine with tubulin as well as ANP with ATPase domain of topoisomerase IIα active sites. Moreover, the radical scavenging potential of the final derivatives was found to be excellent with the range of 0.015–0.630 µM, comparable to the standard ascorbic acid (0.655 µM).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. X. Zhang, K.P. Rakesh, C.S. Shantharam, H.M. Manukumar, A.M. Asiri, H.M. Marwani, H.L. Qin, Bioorg. Med. Chem. 26, 340 (2017)

    Article  Google Scholar 

  2. G.F. Zha, H.L. Qin, B.G.M. Youssif, M.W. Amjad, M.A.G. Raja, A.H. Abdelazeem, S.N.A. Bukhari, Eur. J. Med. Chem. 135, 34 (2017)

    Article  Google Scholar 

  3. H.L. Qin, M.A. Ghafoor Raja, L. Jing, B.G.M. Youssif, M.W. Amjad, S.N.A. Bukhari, M.A. Hussain, Z. Hussain, S.N. Kazmi, Chem. Biol. Drug Des. 90(3), 443 (2017)

    Article  Google Scholar 

  4. J.F. de Oliveira, T.S. Lima, D.B. Vendramini-Costa, S.C.B. de Lacerda Pedrosa, E.A. Lafayette, R.M.F. da Silva, S.M.V. de Almeida, R.O. de Moura, A.L.T.G. Ruiz, J. Ernesto de Carvalho, M.C. Alves de Lima, Eur. J. Med. Chem. 136, 305 (2017)

    Article  Google Scholar 

  5. J.F. de Oliveira, A.L. da Silva, D.B. Vendramini-Costa, C.A. da Cruz Amorim, J.F. Campos, A.G. Ribeiro, R.O. de Moura, J.L. Neves, A.L.T.G. Ruiz, J.E. de Carvalho, M.D.C.A. de Lima, Eur. J. Med. Chem. 104, 148 (2015)

    Article  Google Scholar 

  6. P.R. Kamath, D. Sunil, A.A. Ajees, K.S.R.S. Pai, Bioorg. Chem. 63, 101 (2015)

    Article  Google Scholar 

  7. A. Negi, J.M. Alex, S.M. Amrutkar, A.T. Baviskar, G. Joshi, S. Singh, U.C. Banerjee, R. Kumar, Bioorg. Med. Chem. 23, 5654 (2015)

    Article  Google Scholar 

  8. C. Zhao, K.P. Rakesh, S. Mumtaz, B. Moku, A.M. Asiri, H.M. Marwani, H.M. Manukumar, H.L. Qin, RSC Adv. 8, 9487 (2018)

    Article  Google Scholar 

  9. K.P. Rakesh, C.S. Shantharam, M.B. Sridhara, H.M. Manukumar, H.L. Qin, Med. Chem. Commun. 8, 2023 (2017)

    Article  Google Scholar 

  10. H.L. Qin, Z.P. Shang, I. Jantan, O.U. Tan, M.A. Hussain, M. Sher, S.N.A.Bukhari, RSC Adv. 5, 46330 (2015)

    Article  Google Scholar 

  11. C. Zhao, K. Rakesh, L. Ravidar, W.Y. Fang, Eur. J. Med. Chem. 162, 679 (2019)

    Article  Google Scholar 

  12. K.P. Rakesh, S.M. Wang, J. Leng, L. Ravindar, A.M. Asiri, H.M. Marwani, H.L. Qin, Anticancer Agents Med. Chem. 18(4), 488 (2018)

    Article  Google Scholar 

  13. S.M. Wang, G.F. Zha, K.P. Rakesh, N. Darshini, T. Shubhavathi, H.K. Vivek, N. Mallesha, H.L. Qin, Med. Chem. Commun. 8, 1173 (2017)

    Article  Google Scholar 

  14. H.L. Qin, J. Leng, C.P. Zhang, I. Jantan, M.W. Amjad, M. Sher, M. Naeem-ul-Hassan, M.A. Hussain, S.N.A. Bukhari, J. Med. Chem. 59(7), 3549 (2016)

    Article  Google Scholar 

  15. A. Ozdemir, M.D. Altıntop, G. Turan-Zitouni, G.A. Çiftçi, I. Ertorun, O. Alatas, Z.A. Kaplancıklı, Eur. J. Med. Chem. 89, 304 (2015)

    Article  Google Scholar 

  16. M. Zhang, Q. Chen, G. Yang, Eur. J. Med. Chem. 89, 421 (2015)

    Article  Google Scholar 

  17. N.T. Tzvetkov, S. Hinz, P. Küppers, M. Gastreich, C.E. Müller, J. Med. Chem. 57(15), 6679 (2014)

    Article  Google Scholar 

  18. S. Kumar, S. Mehndiratta, K. Nepali, M.K. Gupta, S. Koul, P.R. Sharma, A.K. Saxena, K.L. Dhar, Org. Med. Chem. Lett. 3(1), 3 (2017)

    Article  Google Scholar 

  19. Z. Datong, X. Rongrong, G. Shoudong, Z. Yaling, Res. Chem. Intermed. 41(9), 6575 (2015)

    Article  Google Scholar 

  20. G. De Martino, M.C. Edler, G. La Regina, A. Coluccia, M.C. Barbera, D. Barrow, R.I. Nicholson, G. Chiosis, G. La Regina, A. Brancale, A. Coluccia, E. Hamel, M. Artico, R. Silvestri, J. Med. Chem. 49, 947 (2006)

    Article  Google Scholar 

  21. S.N. Baytas, N. Inceler, A. Yılmaz, A. Olgac, E. Banoglu, E. Hamel, R. Bortolozzi, G. Viola, S. Menevse, Bioorg. Med. Chem. 22, 3096 (2014)

    Article  Google Scholar 

  22. R.S. Patil, A. Patil, K.D. Beaman, S.A. Patil, Future Med. Chem. 8(11), 1291 (2016)

    Article  Google Scholar 

  23. R. Gastpar, M. Goldbrunner, D. Marko, E. Angerer, J. Med. Chem. 41, 4965 (1998)

    Article  Google Scholar 

  24. D. Kaufmann, M. Pojarova, S. Vogel, R. Liebl, R. Gastpar, D. Gross, T. Nishino, T. Pfaller, E. Angerer, Bioorg. Med. Chem. 15, 5122 (2007)

    Article  Google Scholar 

  25. E.A. Britta, D.B. Scariot, H. Falzirolli, T. Ueda-Nakamura, C.C. Silva, B.P. Dias Filho, R. Borsali, C.V. Nakamura, BMC Microbiol. 14, 236 (2014)

    Article  Google Scholar 

  26. M.A. Souza, S. Juhann, L.A.R.D.S. Lima, F.F. Campos, I.C. Mendes, H. Beraldo, E.M.D. Souza-Fagundes, P.S. Cisalpino, C.A. Rosa, T.M.D.A. Alves, N.P.D. Sa, C.L. Zani, Mem. Inst. Oswaldo Cruz 108(3), 342 (2013)

    Article  Google Scholar 

  27. A.S. Salman, N.A. Mahmoud, M.A. Mohamed, A. Abdel-Aziem, D.M. Elsisi, Am. J. Org. Chem. 6(2), 39 (2016)

    Google Scholar 

  28. S.M.V. de Almeida, E.A. Lafayette, L.P.B.G. da Silva, C.A.D.C. Amorim, T.B. de Oliveira, A.L.T.G. Ruiz, J.E. de Carvalho, R.O. de Moura, E.I.C. Beltrão, M.D.C.A. de Lima, L.B.D.C. Júnior, Int. J. Mol. Sci. 16, 13023 (2015)

    Article  Google Scholar 

  29. B. Xu, Y. Yu, P. Wan, Res. Chem. Intermed. 40, 3095 (2014)

    Article  Google Scholar 

  30. H. Huang, Q. Chen, X. Ku, L. Meng, L. Lin, X. Wang, C. Zhu, Y. Wang, Z. Chen, M. Li, H. Jiang, K. Chen, J. Ding, H. Liu, J. Med. Chem. 53, 3048 (2010)

    Article  Google Scholar 

  31. C. Karaaslan, H. Kadri, T. Coban, S. Suzen, Bioorg. Med. Chem. Lett. 23, 2671 (2013)

    Article  Google Scholar 

  32. V. Mashayekhi, K. Haj Mohammad Ebrahim Tehrani, P. Azerang, S. Sardari, F. Kobarfard, Arch. Pharmacal. Res. 1 (2013)

  33. Z. Liu, S. Wu, Y. Wang, R. Li, J. Wang, L. Wang, Y. Zhao, P. Gong, Eur. J. Med. Chem. 87, 782 (2014)

    Article  Google Scholar 

  34. M. Safavi, N. Esmati, S.K. Ardestani, S. Emami, S. Ajdari, J. Davoodi, A. Shafiee, A. Foroumadi, Eur. J. Med. Chem. 58, 573 (2012)

    Article  Google Scholar 

  35. A.H. Halawa, A.A.E.H. Hassan, M.A. El-Nassag, M.M.A. El-All, G.E.R.A. El-Jaleel, E.M. Eliwa, A.H. Bedair, Eur. J. Chem. 5(1), 111 (2014)

    Article  Google Scholar 

  36. N. Liang, D.D. Kitts, Molecules 19, 19180 (2014)

    Article  Google Scholar 

  37. S. Sepehri, S. Soleymani, R. Zabihollahi, M.R. Aghasadeghi, M. Sadat, L. Saghaie, A. Fassihi, Chem. Biodivers. 14, e1700295 (2017)

    Article  Google Scholar 

  38. M. Safavi, A. Ashtari, F. Khalili, S.S. Mirfazli, M. Saeedi, S. Ardestani, K.P. Ranjbar, R.M.B. Tehrani, B. Larijani, M. Mahdavi, Chem. Biol. Drug Des. 92, 1373 (2018)

    Article  Google Scholar 

  39. M. Volovenko, E.V. Resnyanska, Mendel Commun. 12, 119 (2002)

    Article  Google Scholar 

  40. N. Mahmoodi, S. Ghodsi, Res. Chem. Intermed. 43(2), 661 (2017)

    Article  Google Scholar 

  41. F.A. Momany, R. Rone, J. Comput. Chem. 13, 888 (1992)

    Article  Google Scholar 

  42. http://www.molinspiration.com/cgi-bin/properties

Download references

Acknowledgements

This work was supported by Grants from Isfahan university of Medical Sciences and Tehran University of Medical Sciences.

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran

    Zohreh Bakherad, Afshin Fassihi, Hojjat Sadeghi-Aliabadi & Lotfollah Saghaie

  2. Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, 33535-111, Iran

    Maliheh Safavi

  3. School of Chemistry, Shahrood University of Technology, Shahrood, Iran

    Mohammad Bakherad

  4. Food and Drug Control Laboratories, Food and Drug Laboratory Research Center, MOE and ME, Tehran, Iran

    Hossein Rastegar

  5. Drug Design in Silico Lab, Chemistry Faculty, School of Sciences, University of Tehran, Teheran, Iran

    Jahan B. Ghasemi

  6. Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, 5618953141, Iran

    Saghi Sepehri

  7. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Mahdavi

Authors
  1. Zohreh Bakherad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maliheh Safavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Afshin Fassihi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hojjat Sadeghi-Aliabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mohammad Bakherad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hossein Rastegar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jahan B. Ghasemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Saghi Sepehri
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lotfollah Saghaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mohammad Mahdavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lotfollah Saghaie or Mohammad Mahdavi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Additional information

This paper is dedicated to the memory of our wonderful teacher in Chemistry and Medicinal Chemistry, Professor Abbas Shafiee (1937–2016).

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 2759 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bakherad, Z., Safavi, M., Fassihi, A. et al. Anti-cancer, anti-oxidant and molecular docking studies of thiosemicarbazone indole-based derivatives. Res Chem Intermed 45, 2827–2854 (2019). https://doi.org/10.1007/s11164-019-03765-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11164-019-03765-9

Keywords

Search

Navigation