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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

  • Haiyuan Zhang
  • Ronald Thomas
  • David Oupicky
  • Fangyu Peng
Original Paper

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.

Keywords

Copper Thiosemicarbazone Proliferation inhibition Cell cycle arrest Apoptosis 

Notes

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.

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Copyright information

© SBIC 2007

Authors and Affiliations

  • Haiyuan Zhang
    • 1
    • 2
  • Ronald Thomas
    • 1
  • David Oupicky
    • 3
    • 4
  • Fangyu Peng
    • 1
    • 2
    • 3
    • 5
  1. 1.Carman and Ann Adams Department of PediatricsWayne State UniversityDetroitUSA
  2. 2.Department of RadiologyWayne State UniversityDetroitUSA
  3. 3.Barbara Ann Karmanos Cancer InstituteWayne State UniversityDetroitUSA
  4. 4.School of Medicine, Department of Pharmaceutical SciencesWayne State UniversityDetroitUSA
  5. 5.The PET Center, Children’s Hospital of Michigan, School of MedicineWayne State UniversityDetroitUSA

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