Skip to main content
SpringerLink
Log in

Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Two new copper thiosemicarbazone complexes with an ONNS quadridentate system were synthesized and evaluated for anticancer activity on cisplatin-resistant neuroblastoma cells. Among these two copper complexes, the substituted 8-hydroxyquinoline-2-carboxaldehyde–4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) exhibited stronger cell growth inhibition activity than the unsubstituted copper 8-hydroxyquinoline-2-carboxaldehyde thiosemicarbazide complex (CuHQTS). Both CuHQTS and CuHQDMTS showed dose-dependent cell growth inhibition, cell cycle arrest and apoptosis induction activities on the SK-N-DZ neuroblastoma cells. Increased expression of p53 protein molecules was detected in the SK-N-DZ cells treated with CuHQTS. The data obtained in this study suggest that CuHQDMTS and CuHQTS hold potential as new, effective drugs for treatment of refractory neuroblastoma in children.

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
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Seeger RC, Reynolds CP (1993) In: Holland JF, Frei E, Bast RC, Kufe DW, Morton DL, Weichselbaum RR (eds) Cancer medicine. Lea & Febiger, Philadelphia, pp 2172–2184

    Google Scholar 

  2. Olshan AF, Bunin GR (2000) In: Brodeur GM, Sawada T, Tsuchida Y, Voute PA (eds) Neuroblastoma. Elsevier, New York, pp 33–37

    Google Scholar 

  3. Weir HK, Thun MJ, Hankey BF, Ries LA, Howe HL, Wingo PA, Jemal A, Ward E, Anderson RN, Edwards BK (2003) J Natl Cancer Inst 95:1276–1299

    PubMed  Google Scholar 

  4. Hartmann O, Pinckerton CR, Philip T, Zucker JM, Breatnach F (1988) J Clin Oncol 6:44–50

    PubMed  CAS  Google Scholar 

  5. Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, Fojo T (1996) Biochem Pharmacol 52:1855–1865

    Article  PubMed  CAS  Google Scholar 

  6. Niethammer D, Handgretinger R (1995) Eur J Cancer 31:568–571

    Article  Google Scholar 

  7. Finch RA, Liu MC, Cory AH, Cory JG, Sartorelli AC (1999) Adv Enzyme Regul 39:3–12

    Article  PubMed  CAS  Google Scholar 

  8. Rappa G, Lorico A, Liu MC, Kruh GD, Cory AH, Cory JG, Sartorelli AC (1997) Biochem Pharmacol 54:649–655

    Article  PubMed  CAS  Google Scholar 

  9. Liu MC, Lin TS, Cory JG, Cory AH, Sartorelli AC (1996) J Med Chem 39:2586–2593

    Article  PubMed  CAS  Google Scholar 

  10. Cory JG, Cory AH, Rappa G, Lorico A, Liu MC, Lin TS, Sartorelli AC (1994) Biochem Pharmacol 48:335–344

    Article  PubMed  CAS  Google Scholar 

  11. Kolocouris A, Dimas K, Pannecouque C, Witvrouw M, Foscolos G, Stamatiou G, Fytas G, Zoidis G, Kolocouris N, Andrei G, Snoeck R (2002) Bioorg Med Chem 12:723–727

    Article  CAS  Google Scholar 

  12. Afrasiabi Z, Sinn E, Padhye S, Dutta S, Newton C, Anson CE, Powell AK (2003) J Inorg Biochem 95:306–314

    Article  PubMed  CAS  Google Scholar 

  13. Belicchi-Ferrari M, Bisceglie F, Casoli C, Duro S, Morgenstern-Badarau I, Pelosi G, Pilotti E, Pinelli S, Tarasconi P (2005) J Med Chem 48:1671–1675

    Article  PubMed  CAS  Google Scholar 

  14. Richardson DR, Sharpe PP, Lovejoy DB, Senaratne D, Kalinowski DS, Islam M, Bernhardt PV (2006) J Med Chem 49:6510–6521

    Article  PubMed  CAS  Google Scholar 

  15. Easmon J, Purstinger G, Heinisch G, Roth T, Fiebig HH, Holzer W, Jager W, Jenny M, Hofmann J (2001) J Med Chem 44:2164–2171

    Article  PubMed  CAS  Google Scholar 

  16. Baldini M, Belicchi-Ferrari M, Bisceglie F, Pelosi G, Pinelli S, Tarasconi P (2004) Inorg Chem 43:7170–7179

    Article  PubMed  CAS  Google Scholar 

  17. Aguirre MC, Borras J, Castineiras A, Garcia-Monteagudo JM, Garcia-Santos I, Niclos J, West DX (2006) Eur J Inorg Chem 6:1231–1244

    Article  Google Scholar 

  18. Hu W, Zhou W, Xia C, Wen X (2006) Bioorg Med Chem Lett 16:2213–2218

    Article  PubMed  CAS  Google Scholar 

  19. Baldini M, Belicchi-Ferrari M, Bisceglie F, Pelosi G, Pinelli S, Tarasconi P (2003) Inorg Chem 42:2049–2055

    Article  PubMed  CAS  Google Scholar 

  20. Padhye S, Kauffman GB (1985) Coord Chem Rev 63:127–160

    Article  CAS  Google Scholar 

  21. Saryan LA, Ankel E, Krishnamuri C, Petering DH, Elford H (1979) J Med Chem 22:1218–1221

    Article  PubMed  CAS  Google Scholar 

  22. Scovill JP, Klayman DL, Franchino CF (1982) J Med Chem 25:1261–1264

    Article  PubMed  CAS  Google Scholar 

  23. Brlicchi-Ferrari M, Bisceglie F, Pelosi G, Tarasconi P, Albertini R, Pinelli S (2001) J Inorg Biochem 87:137–147

    Article  Google Scholar 

  24. Miller MC, Stineman CN, Vance JR, West DX, Hall IH (1998) Anticancer Res 18:4131–4139

    PubMed  CAS  Google Scholar 

  25. Garcia-Tojal J, Garcia-Orad A, Diaz AA, Serra JL, Urtiaga MK, Arriortua MI, Rojo T (2001) J Inorg Biochem 84:271–278

    Article  PubMed  CAS  Google Scholar 

  26. Afrasiabi Z, Sinn E, Kulkarni PP, Ambike V, Padhye S, Deobagakar D, Heron M, Gabbutt C, Anson CE, Powell AK (2005) Inorg Chim Acta 358:2023–2030

    Article  CAS  Google Scholar 

  27. Chikate RC, Belapure AR, Padhye SB, West DX (2005) Polyhedron 24:889–899

    Article  CAS  Google Scholar 

  28. Kowol CR, Berger R, Eichinger R, Roller A, Jakupee MA, Schmidt PP, Arion VB, Keppler BK (2007) J Med Chem 50:1254–1265

    Article  PubMed  CAS  Google Scholar 

  29. Shakya R, Peng F, Liu J, Heeg MJ, Verani CN (2006) Inorg Chem 45:6263–6268

    Article  PubMed  CAS  Google Scholar 

  30. Chen D, Peng F, Cui QZ, Daniel KG, Orlu S, Liu J, Dou QP (2005) Front Biosci 10:2932–2939

    Article  PubMed  CAS  Google Scholar 

  31. Burnette WN (1981) Anal Biochem 112:195–203

    Article  PubMed  CAS  Google Scholar 

  32. Garge PL, Chikate RC, Padhye SB, Savariault JM, Loth P, Tuchagues JP (1990) Inorg Chem 29:3315–3320

    Article  CAS  Google Scholar 

  33. Labisbal E, Haslow KD, Pedrares AS, Martines JV, Ortega SH, West DX (2003) Polyhedron 22:2831–2837

    Article  CAS  Google Scholar 

  34. Wang M, Wang L, Li YZ, Li QX, Xu ZD, Qu DM (2001) Transition Met Chem 26:307–310

    Article  CAS  Google Scholar 

  35. Jouad EM, Riou A, Allain M, Khan MA, Bouct GM (2001) Polyhedron 20:67–74

    Article  CAS  Google Scholar 

  36. Ferrari MB, Bonardi A, Fava GG, Pelizzi C, Tarasconi P (1994) Inorg Chem Acta 223:77–86

    Article  Google Scholar 

  37. West DX, Lockwood MA, Albert JN, Liberta AE (1991) Spectrochim Acta A 49:1809–1816

    Article  Google Scholar 

  38. West DX, Salberg MM, Bain GA, Liberta AE, Valdesmartinez J, Fermandez-Ortega SJ (1996) Transition Met Chem 21:206–212

    Article  CAS  Google Scholar 

  39. West DX, Yang Y, Klein TL, Goldberg KI, Liberta AE, Valdes-Martinez J, Toscano RA (1995) Polyhedron 14:1681–1693

    Article  CAS  Google Scholar 

  40. Moore EC, Zedeck MS, Agrawal KC, Sartorelli AC (1970) Biochemistry 9:4492–4498

    Article  PubMed  CAS  Google Scholar 

  41. Thelander L, Graslund A (1983) J Biol Chem 258:4063–4066

    PubMed  CAS  Google Scholar 

  42. Kaska W, Carrano C, Michalowski J, Jackson J, Levinson W (1978) Bioinorg Chem 8:225–236

    Article  PubMed  CAS  Google Scholar 

  43. Bymes RW, Mohan M, Antholine WE, Xu RX, Petering DH (1990) Biochemistry 29:7046–7053

    Article  Google Scholar 

  44. Bennet MR (1999) Biochem Pharmcol 58:1089–1095

    Article  Google Scholar 

  45. Filomeni G, Cerchiaro G, Ferreira C, Martino A, Pedersen JZ, Rotilio G, Ciriolo MR (2007) J Biol Chem 282:12010–12021

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Claudio Verani for help in chemical characterization of the complexes and Jiu-sheng Wu for technical assistance. This project was partly funded by a faculty research development award from the Carman and Ann Adams Foundation and a new investigator award from Fighting Children’s Cancer Foundation to Fangyu Peng.

Author information

Authors and Affiliations

  1. Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, MI, USA

    Haiyuan Zhang, Ronald Thomas & Fangyu Peng

  2. Department of Radiology, Wayne State University, Detroit, MI, USA

    Haiyuan Zhang & Fangyu Peng

  3. Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    David Oupicky & Fangyu Peng

  4. School of Medicine, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI, USA

    David Oupicky

  5. The PET Center, Children’s Hospital of Michigan, School of Medicine, Wayne State University, 3901 Beaubien Blvd, Detroit, MI, 48201, USA

    Fangyu Peng

Authors
  1. Haiyuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ronald Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Oupicky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fangyu Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fangyu Peng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, H., Thomas, R., Oupicky, D. et al. Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells. J Biol Inorg Chem 13, 47–55 (2008). https://doi.org/10.1007/s00775-007-0299-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-007-0299-6

Keywords

Search

Navigation