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Anticancer and DNA Binding Activities of Platinum (IV) Complexes; Importance of Leaving Group Departure Rate

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Abstract

The two six-coordinate Pt(IV) complexes, containing bidentate nitrogen donor/methyl ligands with general formula [Pt(X)2Me2(tbu2bpy)], where tbu2bpy = 4,4′-ditert-butyl-2,2′-bipyridine and X = Cl (C1) or Br (C2), serving as the leaving groups were synthesized for evaluation of their anticancer activities and DNA binding properties. To examine anticancer activities of the synthetic complexes, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ethidium bromide/acridine orange (EB/AO) staining method were performed. The binding properties of these complexes to DNA and purine nucleotides were examined, using different spectroscopic techniques. These complexes demonstrated significant anticancer activities against three cancer cell lines Jurkat, K562, and MCF-7. On the basis of the results of EB/AO staining, C1 and C2 were also capable to induce apoptosis in cancer cells. These complexes comprise halide leaving groups, displaying different departure rates; accordingly, they demonstrated slightly dissimilar anticancer activity and significantly different DNA/purine nucleotide binding properties. The results of DNA interaction studies of these complexes suggest a mixed-binding mode, comprising partial intercalation and groove binding. Overall, the results presented herein indicate that the newly synthesized Pt(IV) complexes are promising class of the potential anticancer agents which can be considered as molecular templates in designing novel platinum anticancer drugs. This study also highlights the importance of leaving group in anticancer activity and DNA binding properties of Pt(IV) complexes.

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Acknowledgments

We would like to acknowledge the financial supports of research council of Shiraz University for this study. Also the supports of Iran National Science Foundation (grant nos. 92001695 and 90005876) are acknowledged.

Conflict of Interest

The authors declared no conflicts of interest.

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Authors and Affiliations

  1. Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran

    Zahra Pouryasin & Reza Yousefi

  2. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran

    S. Masoud Nabavizadeh, Mehdi Rashidi & Peyman Hamidizadeh

  3. Department of Chemistry, Shiraz University of Technology, Shiraz, Iran

    Mohammad-Mehdi Alavianmehr

  4. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

    Ali Akbar Moosavi-Movahedi

Authors
  1. Zahra Pouryasin
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  2. Reza Yousefi
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  3. S. Masoud Nabavizadeh
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  4. Mehdi Rashidi
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  5. Peyman Hamidizadeh
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  6. Mohammad-Mehdi Alavianmehr
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  7. Ali Akbar Moosavi-Movahedi
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Correspondence to Reza Yousefi.

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Pouryasin, Z., Yousefi, R., Nabavizadeh, S.M. et al. Anticancer and DNA Binding Activities of Platinum (IV) Complexes; Importance of Leaving Group Departure Rate. Appl Biochem Biotechnol 172, 2604–2617 (2014). https://doi.org/10.1007/s12010-013-0700-6

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  • DOI: https://doi.org/10.1007/s12010-013-0700-6

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