Skip to main content
SpringerLink
Log in

The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The development of resistance and unwanted harmful interaction with other biomolecules instead of DNA are the major drawbacks for application of platinum (Pt) complexes in cancer chemotherapy. To conquer these problems, much works have been done so far to discover innovative Pt complexes. The objective of the current study was to evaluate the anti cancer activities of a series of four and five-coordinated Pt(II) complexes, having deprotonated 2-phenyl pyridine (abbreviated as C^N), biphosphine moieties, i.e., dppm = bis(diphenylphosphino) methane (Ph2PCH2PPh2) and dppa = bis(diphenylphosphino)amine (Ph2PNHPPh2), as the non-leaving carrier groups. The growth inhibitory effect of the Pt complexes [Pt(C^N)(dppm)]PF6: C 1 , [Pt(C^N)(dppa)]PF6: C 2 , and [Pt(C^N)I(dppa)]: C 3 , toward the cancer cell lines was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In addition, the florescence quenching experiments of the interaction between human serum albumin (HSA) and the Pt complexes were performed in order to obtain the binding parameters and to evaluate the denaturing properties of these complexes upon binding to the general carrier protein of blood stream. The structure–activity relationship studies reveal that four-coordinated Pt complexes C 1 and C 2 with both significant hydrophobic and charge characteristics, not only exhibit strong antiproliferation activity toward the cancer cell lines, but also they display lower denaturing effect against carrier protein HSA. On the other hand, five-coordinated C 3 complex with the unusual intermolecular NH…Pt hydrogen binding and the intrinsic ability for oligomerization, exhibits poor anticancer activity and strong denaturing property. The current study reveals that the balance between charge and hydrophobicity of the Pt complexes, also their hydrogen binding abilities and coordination mode are important for their anticancer activities. Moreover, this study may suggest C 1 and C 2 as the potential template structures for synthesis of new generation of four-coordinated Pt complexes with strong anticancer activities and weak denaturing effects against proteins.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Utuku, S., Gumus, F., Karaoglu, T., & Özkul, A. (2007). Journal of Faculty of Pharmacy of Ankara, 36, 21–30.

    Google Scholar 

  2. Alvarez-Valdés, A., Manual Pérez, J., López-Solera, I., Lannegrand, R., Continente, J. M., Amo-Ochoa, P., et al. (2002). Journal of Medicinal Chemistry, 45, 1835–1844.

    Article  Google Scholar 

  3. Foltinova, V., Švihálková Šindlerová, L., Horváth, V., Sova, P., Hofmanová, J., Janisch, R., et al. (2008). Scripta Medica (BRNO), 81, 105–116.

    Google Scholar 

  4. Bakalova, A., Varbanov, H., Buyukliev, R., Momekov, G., Ivanov, D., & Doytchinova, I. (2010). Archiv der Pharmazie (Weinheim) (Epub ahead of print).

  5. Hall, M. D., Amjadi, A., Zhang, M., Beale, P. J., & Hambley, T. W. (2004). Journal of Inorganic Biochemistry, 98, 1614–1624.

    Article  CAS  Google Scholar 

  6. Kostova, I. (2006). Recent Patents on Anti-Cancer Drug Discovery, 1, 1–22.

    Article  CAS  Google Scholar 

  7. Lippert, B. (Ed.). (1999). Cisplatin: chemistry and biochemistry of a leading anticancer drug. Zürich: Wiley VCH.

    Google Scholar 

  8. Chijiwa, S., Masutani, C., Hanaoka, F., Iwai, S., & Kuraoka, I. (2010). Carcinogenesis, 31, 388–393.

    Article  CAS  Google Scholar 

  9. Manic, S., Gatti, L., Carenini, N., Fumagalli, G., Zunino, F., & Perego, P. (2003). Current Cancer Drug Targets, 3, 21–29.

    Article  CAS  Google Scholar 

  10. Sedletska, Y., Giraud-Panis, M. J., & Malinge, J. M. (2005). Current Medicinal Chemistry. Anti-Cancer Agents, 5, 251–265.

    Article  CAS  Google Scholar 

  11. Jordan, P., & Carmo-Fonseca, M. (1990). Cellular and Molecular Life Sciences, 57, 1229–1235.

    Article  Google Scholar 

  12. Kim, W. K., & Kwon, Y. E. (2007). Cancer Chemotheraphy and Pharmacology, 60, 237–243.

    Article  CAS  Google Scholar 

  13. Siddik, Z. H. (2003). Oncogene, 22, 7265–7279.

    Article  CAS  Google Scholar 

  14. Mandal, R., Kalke, R., & Li, X. F. (2004). Chemical Research in Toxicology, 17, 1391–1397.

    Article  CAS  Google Scholar 

  15. Boisdron-Celle, M., Lebouil, A., Allain, P., & Gamelin, E. (2001). Bulletin du Cancer, 8, 814–819.

    Google Scholar 

  16. Litterst, C. L. (1984). Agents and Actions, 15, 520–524.

    Article  CAS  Google Scholar 

  17. Litterst, C. L., & Schweitzer, V. G. (1988). Research Communications in Chemical Pathology and Pharmacology, 61, 35–48.

    CAS  Google Scholar 

  18. Kasherman, Y., Sturup, S., & Gibson, D. (2009). Journal of Medicinal Chemistry, 52, 4319–4328.

    Article  CAS  Google Scholar 

  19. Stewart, D. J. (2007). Critical Reviews in Oncology/Hematology, 63, 12–31.

    Article  Google Scholar 

  20. Galanski, M., Arion, V. B., Jakupec, M. A., & Kepler, B. K. (2003). Current Pharmaceutical Design, 9, 2078–2089.

    Article  CAS  Google Scholar 

  21. Kwon, Y. E., Whang, K., Park, Y., & Kim, K. H. (2003). Bioorganic & Medicinal Chemistry, 11, 1669–1676.

    Article  CAS  Google Scholar 

  22. Lazić, J. M., Vucićević, L., Grgurić-Sipka, S., Janjetović, K., Kaluderović, G. N., Misirkić, M., et al. (2010). ChemMedChem, 5, 881–889.

    Article  Google Scholar 

  23. Silva, H., Barra, C. V., Rocha, F. V., de Almeida, M. V., Cesar, E. T., da Silva Siqueira, L. M., et al. (2010). Chemical Biology & Drug Design, 75, 407–411.

    Article  CAS  Google Scholar 

  24. Farrell, N., Qu, S. Y., & Hacker, M. P. (1990). Journal of Medicinal Chemistry, 33, 2179–2184.

    Article  CAS  Google Scholar 

  25. Wheate, N. J., & Collins, J. G. (2005). Current Medicinal Chemistry. Anti-Cancer Agents, 5, 267–279.

    Article  CAS  Google Scholar 

  26. Vondálová Blanárová, O., Jelínková, I., Szöor, A., Skender, B., Soucek, K., Horváth, V., et al. (2011). Carcinogenesis, 32, 42–51.

    Article  Google Scholar 

  27. van der Vusse, G. J. (2009). Drug Metabolism and Pharmacokinetics, 24, 300–307.

    Article  Google Scholar 

  28. Lu, J., Stewart, A. J., Sadler, P. J., Pinheiro, T. J., & Blindauer, C. A. (2008). Biochemical Society Transactions, 36, 1317–1321.

    Article  CAS  Google Scholar 

  29. Mosmann, T. (1983). Journal of Immunological Methods, 65, 55–63.

    Article  CAS  Google Scholar 

  30. Hawe, A., Poole, R., & Jiskoot, W. (2010). Analytical Biochemistry, 401, 99–106.

    Article  CAS  Google Scholar 

  31. Gao, L. M., Li, R. C., & Wang, K. (1989). Journal of Inorganic Biochemistry, 36, 83–92.

    Article  CAS  Google Scholar 

  32. Frezza, M., Dou, Q. P., Xiao, Y., Samouei, H., Rashidi, M., Samari, F., et al. (2011). Journal of Medicinal Chemistry, 54(18), 6166–6176.

    CAS  Google Scholar 

  33. Teixeira, L. J., Seabra, M., Reis, E., Teresa, M., Cruz, G. D., Pedroso de Lima, M. C., et al. (2004). Journal of Medicinal Chemistry, 47, 2917–2925.

    Article  CAS  Google Scholar 

  34. Marques, M. P. M., Gira, T. O., Maria, C., De Lima, P., Gameiro, A., Pereira, E., et al. (2002). Biochimica et Biophysica Acta, 1589, 63–70.

    Article  CAS  Google Scholar 

  35. Benedetti, M., Malina, J., Kasparkova, J., Brabec, V., & Natile, G. (2010). Biotechnology and Molecular Biology, 5, 38–45.

    Google Scholar 

  36. Tiekink, E. R. T. (2008). InflammoPharmacology, 16, 138–142.

    Article  CAS  Google Scholar 

  37. Rabindra Reddy, P. (2010). Indian Journal of Chemistry, 49, 1003–1015.

    Google Scholar 

  38. Lasic, D. D., Che, B., Stuart, M. C., Guo, L., Frederik, P. M., & Barenholz, Y. (1995). Biochimica et Biophysica Acta, 1239, 145–156.

    Article  Google Scholar 

  39. Gately, D. P., & Howell, S. B. (1993). British Journal of Cancer, 67, 1171–1176.

    Article  CAS  Google Scholar 

  40. Abu-Surrah, A. S., & Kettunen, M. (2006). Current Medicinal Chemistry, 13, 1337–1357.

    Article  CAS  Google Scholar 

  41. Poliseno, L., Mariani, L., Collecchi, P., Piras, A., Zaccaro, L., & Rainaldi, G. (2002). Cancer Chemotherapy and Pharmacology, 50, 127–130.

    Article  CAS  Google Scholar 

  42. Ding, F., Wei, L., Xi, Z., Li-Jun, W., Li, Z., & Ying, S. (2010). Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 75, 1088–1094.

    Article  Google Scholar 

  43. Bordbar, A. K., & Taheri-Kafrani, A. (2007). Colloids and Surfaces. B, Biointerfaces, 55, 84–89.

    Article  CAS  Google Scholar 

  44. Chang-Ying, Y., An-Xin, H., Yi, L., Hui, T., & Song-Sheng, Q. (2005). Journal of Pharmaceutical and Biomedical Analysis, 39, 263–2677.

    Article  Google Scholar 

  45. Wang, T., Xiang, B., Wang, Y., Chen, C., Dong, Y., Fang, H., et al. (2008). Colloids and Surfaces. B, Biointerfaces, 65, 113–119.

    Article  CAS  Google Scholar 

  46. Ajloo, D., Behnam, H., Saboury, A. A., Mohamadi-Zonoz, F., Ranjbar, B., Moosavi-Movahedi, A. A., et al. (2007). Bulletin of the Korean Chemical Society, 28, 730–736.

    Article  CAS  Google Scholar 

  47. Froehlich, E., Mandeville, J. S., Jennings, C. J., Sedaghat-Herati, R. C., & Tajmir-Riahi, H. A. (2009). The Journal of Physical Chemistry. B, 113, 6986–6993.

    Article  CAS  Google Scholar 

  48. Semisotnov, G. V., Rodionova, N. A., Razgulyaev, O. I., Uversky, V. N., Gripas, A. F., & Gilmanshin, R. I. (1991). Biopolymers, 31, 119–128.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

R.Y. would like to thank financial support of Iran National Science Foundation (INSF)-Grant nos. 88001578. In addition, the support of research council of Shiraz University is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, 71454, Iran

    Reza Yousefi, Sadaf Aghevlian, Fatemeh Mokhtari, Zohreh Tavaf & Zahra Pouryasin

  2. Department of Mechanical Engineering, College of Engineering, Shiraz University, Shiraz, Iran

    Sadaf Aghevlian

  3. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, 71454, Iran

    Hamidreza Samouei, Mehdi Rashidi & S. Masoud Nabavizadeh

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

    Fatemeh Mokhtari & Mohammad Mehdi Papari

  5. Institute of Biotechnology, Shiraz University, Shiraz, Iran

    Reza Yousefi & Ali Niazi

  6. Nuclear Engineering department and Radiation Research center, College of Engineering, Shiraz University, Shiraz, Iran

    Reza Faghihi

Authors
  1. Reza Yousefi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sadaf Aghevlian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatemeh Mokhtari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hamidreza Samouei
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Rashidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Masoud Nabavizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zohreh Tavaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zahra Pouryasin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ali Niazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Reza Faghihi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mohammad Mehdi Papari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Reza Yousefi or Mehdi Rashidi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yousefi, R., Aghevlian, S., Mokhtari, F. et al. The Anticancer Activity and HSA Binding Properties of the Structurally Related Platinum (II) Complexes. Appl Biochem Biotechnol 167, 861–872 (2012). https://doi.org/10.1007/s12010-012-9733-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-012-9733-5

Keywords

Search

Navigation