Skip to main content

Advertisement

SpringerLink
Log in

Improving of Anticancer Activity and Solubility of Cisplatin by Methylglycine and Methyl Amine Ligands Against Human Breast Adenocarcinoma Cell Line

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

Abstract

Methylglycine, also known sarcosine, is dramatically used in drug molecules and its metal complexes can interact to DNA and also do cleavage. Hence, to study the influence of methylglycine ligand on biological behavior of metal complexes, two water-soluble platinum (II) complexes with the formula cis-[Pt(NH3)2(CH3-gly)]NO3 and cis-[Pt(NH2-CH3)2(CH3-gly)]NO3 (where CH3-gly is methylglycine) have been synthesized and characterized by spectroscopic methods, molar conductivity measurements, and elemental analyzes. The anticancer activity of synthesized complexes was tested against human breast adenocarcinoma cell line of MCF7 using MTT assay and results showed excellent anticancer activity with Cc50 values of 126 and 292 μM after 24 h incubation time, for both complexes of cis-[Pt(NH3)2(CH3gly)]NO3 and cis-[Pt(NH2-CH3)2(CH3gly)]NO3, respectively. Also, the interaction between Pt(II) complexes with calf thymus DNA was extensively studied by means of absorption spectroscopy, fluorescence titration spectra displacement with ethidium bromide (EtBr), and circular dichroism studied in Tris-buffer. The obtained spectroscopic results revealed that two complexes can bind to highly polymerized calf thymus DNA cooperatively and denature at micromolar concentrations. The fluorescence data indicate that quenching effect for cis-[Pt(NH3)2(CH3gly)]NO3 (Ksv = 9.48 mM−1) was higher than that of cis-[Pt(NH2-CH3)2(CH3gly)]NO3 (Ksv = 1.98 mM−1). These results were also confirmed by circular dichrosim spectra. Consequently, docking data showed that cis-[Pt(NH3)2(CH3gly)]NO3 with more interaction energy binds on DNA via groove binding which is more compatible with experimental results.

ᅟ

Two anticancer Pt(II) complexes, cis-[Pt(NH3)2(CH3gly)]NO3 and cis-[Pt(NH2−CH3)2(CH3gly)]NO3, have been synthesized and interacted with calf thymus DNA. Improving solubility of these compounds reduce side effects and increase anticancer activity against human breast cell line. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. Results show that both Pt(II) complexes can interact to DNA via groove binding.

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

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

Similar content being viewed by others

Abbreviations

CT-DNA:

Calf thymus DNA

Methylgly:

Methyl glycine

CD:

Circular dichroism

EB:

Ethidium bromide

References

  1. Weaver, A., Flemming, S., Kish, J., Vandenberg, H., Jacob, J., Crissman, J., & Al-Sarraf, M. (1982). Cis-platinum and 5-fluorouracil as induction therapy for advanced head and neck cancer. The American Journal of Surgery, 144(4), 445–448.

    Article  CAS  PubMed  Google Scholar 

  2. Storr, T., Thompson, K. H., & Orvig, C. (2006). Design of targeting ligands in medicinal inorganic chemistry. Chemical Society Reviews, 35(6), 534–544.

    Article  CAS  PubMed  Google Scholar 

  3. Farrell, N. (2015). Multi-platinum anti-cancer agents. Substitution-inert compounds for tumor selectivity and new targets. Chemical Society Reviews, 44(24), 8773–8785.

    Article  CAS  PubMed  Google Scholar 

  4. Deubel, D. V. (2004). Factors governing the kinetic competition of nitrogen and sulfur ligands in cisplatin binding to biological targets. Journal of the American Chemical Society, 126(19), 5999–6004.

    Article  CAS  PubMed  Google Scholar 

  5. Yousefi, R., Aghevlian, S., Mokhtari, F., Samouei, H., Rashidi, M., Nabavizadeh, S. M., Tavaf, Z., Pouryasin, Z., Niazi, A., Faghihi, R., & Papari, M. M. (2012). The anticancer activity and HSA binding properties of the structurally related platinum (II) complexes. Applied Biochemistry and Biotechnology, 167(4), 861–872.

    Article  CAS  PubMed  Google Scholar 

  6. Barabas, K., Milner, R., Lurie, D., & Adin, C. (2008). Cisplatin: a review of toxicities and therapeutic applications. Veterinary and Comparative Oncology, 6(1), 1–18.

    Article  CAS  PubMed  Google Scholar 

  7. Wu, G. (2009). Amino acids: metabolism, functions, and nutrition. Amino Acids, 37(1), 1–17.

    Article  CAS  PubMed  Google Scholar 

  8. Gentilucci, L., De Marco, R., & Cerisoli, L. (2010). Chemical modifications designed to improve peptide stability: incorporation of non-natural amino acids, pseudo-peptide bonds, and cyclization. Current Pharmaceutical Design, 16(28), 3185–3203.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao, M., Yang, M., Li, X.-M., Jiang, P., Baranov, E., Li, S., & Hoffman, R. M. (2005). Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proceedings of the National Academy of Sciences of the United States of America, 102(3), 755–760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gorre, M. E., Mohammed, M., Ellwood, K., Hsu, N., Paquette, R., Rao, P. N., & Sawyers, C. L. (2001). Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science, 293(5531), 876–880.

    Article  CAS  PubMed  Google Scholar 

  11. Eslami Moghadam, M., Saidifar, M., Divsalar, A., Mansouri-Torshizi, H., Saboury, A. A., Farhangian, H., & Ghadamgahi, M. (2016). Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt (II) and Pd (II) complexes of glycine derivatives with calf thymus DNA. Journal of Biomolecular Structure and Dynamics, 34(1), 206–222.

    Article  CAS  PubMed  Google Scholar 

  12. Safa Shams Abyaneh, F., Eslami Moghadam, M., Hoseini Sadr, M., & Divsalar, A. (2017). Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog. Journal of Biomolecular Structure and Dynamics, 1–13. https://doi.org/10.1080/07391102.2017.1301273.

  13. Ajloo, D., Moghadam, M. E., Ghadimi, K., Ghadamgahi, M., Saboury, A. A., Divsalar, A., & Yousefi, K. (2015). Synthesis, characterization, spectroscopy, cytotoxic activity and molecular dynamic study on the interaction of three palladium complexes of phenanthroline and glycine derivatives with calf thymus DNA. Inorganica Chimica Acta, 430, 144–160.

    Article  CAS  Google Scholar 

  14. Kantoury, M., Eslami Moghadam, M., Tarlani, A. A., & Divsalar, A. (2016). Structure effect of some new anticancer Pt (II) complexes of amino acid derivatives with small branched or linear hydrocarbon chains on their DNA interaction. Chemical Biology & Drug Design, 88(1), 76–87.

    Article  CAS  Google Scholar 

  15. Heydari, M., Moghadam, M. E., Tarlani, A., & Farhangian, H. (2017). DNA as a target for anticancer phen-imidazole Pd (II) complexes. Applied Biochemistry and Biotechnology, 182(1), 110–127.

    Article  CAS  PubMed  Google Scholar 

  16. Lippert, B. (1999). Cisplatin: chemistry and biochemistry of a leading anticancer drug. Zürich: John Wiley & Sons, Verlag Helvetica Chimica Acta.

  17. Hadian Rasanani, S., Eslami Moghadam, M., Soleimani, E., Divsalar, A., & Tarlani, A. (2017). Improving activity of anticancer oxalipalladium analog by the modification of oxalate group with isopentylglycine. Journal of Coordination Chemistry, 70(22), 3769–3789.

    Article  CAS  Google Scholar 

  18. Eslami Moghadam, M., Divsalar, A., Abolhosseini Shahrnoy, A., & Saboury, A. A. (2016). Synthesis, cytotoxicity assessment, and interaction and docking of novel palladium (II) complexes of imidazole derivatives with human serum albumin. Journal of Biomolecular Structure and Dynamics, 34(8), 1751–1762.

    Article  CAS  PubMed  Google Scholar 

  19. Mansouri-Torshizi, H., Shahraki, S., Nezami, Z. S., Ghahghaei, A., Najmedini, S., Divsalar, A., Ghaemi, H., & Saboury, A.-A. (2014). Platinum (II)/palladium (II) complexes with n-propyldithiocarbamate and 2, 2′-bipyridine: synthesis, characterization, biological activity and interaction with calf thymus DNA. Complex Metals, 1(1), 23–31.

    Article  CAS  Google Scholar 

  20. Yakovchuk, P., Protozanova, E., & Frank-Kamenetskii, M. D. (2006). Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Research, 34(2), 564–574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mansouri-Torshizi, H., Saeidifar, M., Divsalar, A., & Saboury, A. A. (2010). Interaction studies between a 1, 10-phenanthroline adduct of palladium (II) dithiocarbamate anti-tumor complex and calf thymus DNA. A synthesis spectral and in-vitro study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 77(1), 312–318.

    Article  CAS  Google Scholar 

  22. Shahabadi, N., Kashanian, S., & Darabi, F. (2009). In vitro study of DNA interaction with a water-soluble dinitrogen Schiff base. DNA and Cell Biology, 28(11), 589–596.

    Article  CAS  PubMed  Google Scholar 

  23. Macquet, J. P., & Butour, J. L. (1978). A circular dichroism study of DNA· platinum complexes. The FEBS Journal, 83(2), 375–387.

    CAS  Google Scholar 

  24. Sullivan, E. (1979). Circular dichroism of palladium (II) and platinum (II) diamine complexes. Canadian Journal of Chemistry, 57(1), 67–70.

    Article  CAS  Google Scholar 

  25. Ajloo, D., Yoonesi, B., & Soleymanpour, A. (2010). Solvent effect on the reduction potential of anthraquinones derivatives. The experimental and computational studies. International Journal of Electrochemical Science, 5, 459–477.

    CAS  Google Scholar 

  26. Saeidifar, M., Mansouri-Torshizi, H., Palizdar, Y., Divsalar, A., & Saboury, A. A. (2013). Synthesis, characterization, and cytotoxicity studies of a novel palladium (II) complex and evaluation of DNA-binding aspects. Nucleosides, Nucleotides and Nucleic Acids, 32(7), 366–388.

    Article  CAS  PubMed  Google Scholar 

  27. Shahraki, S., Mansouri-Torshizi, H., Heydari, A., Ghahghaei, A., Divsalar, A., Saboury, A., et al. (2015). Platinum (II) and palladium (II) complexes with 1, 10-phenanthroline and pyrrolidinedithiocarbamato ligands: synthesis, DNA-binding and anti-tumor activity in leukemia K562 cell lines. Iranian Journal of Science and Technology, 39(A2), 187.

    Google Scholar 

  28. Aminzadeh, M., Mansouri-Torshizi, H., & Modarresi-Alam, A. R. (2016). 2, 2′-bipyridine coplanar with coordination square of Pd (II) nonyldithiocarbamato antitumor complex interacting with DNA in two distinct steps. Journal of Biomolecular Structure and Dynamics, 35, 1–13.

    Google Scholar 

  29. Saeidifar, M., Mansouri-Torshizi, H., Palizdar, Y., Eslami-Moghaddam, M., Divsalar, A., & Saboury, A. A. (2014). Synthesis, characterization, cytotoxicity and DNA binding studies of a novel anionic organopalladium (II) complex. Acta Chimica Slovenica, 61(1), 126–136.

    CAS  PubMed  Google Scholar 

  30. Mansouri-Torshizi, H., Saeidifar, M., Khosravi, F., Divsalar, A., Saboury, A. A., & Hassani, F. (2011). DNA binding and antitumor activity of α-diimineplatinum (II) and palladium (II) dithiocarbamate complexes. Bioinorganic Chemistry and Applications, 2011, 1–11.

    Article  CAS  Google Scholar 

  31. Marmur, J., & Doty, P. (1962). Determination of the base composition of deoxyribonucleic acid from its thermal denaturation temperature. Journal of Molecular Biology, 5(1), 109–118.

    Article  CAS  PubMed  Google Scholar 

  32. Mansouri-Torshizi, H., Saeidifar, M., Divsalar, A., & Saboury, A. (2011). Study on interaction of DNA from calf thymus with 1, 10-phenanthrolinehexyldithiocarbamatopalladium (II) nitrate as potential antitumor agent. Journal of Biomolecular Structure and Dynamics, 28(5), 805–814.

    Article  CAS  PubMed  Google Scholar 

  33. Shahabadi, N., Kashanian, S., & Purfoulad, M. (2009). DNA interaction studies of a platinum (II) complex, PtCl 2 (NN)(NN= 4, 7-dimethyl-1, 10-phenanthroline), using different instrumental methods. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 72(4), 757–761.

    Article  CAS  Google Scholar 

  34. Ware, W. R. (1962). Oxygen quenching of fluorescence in solution: an experimental study of the diffusion process. The Journal of Physical Chemistry, 66(3), 455–458.

    Article  CAS  Google Scholar 

  35. Shahabadi, N., Maghsudi, M., Mahdavi, M., & Pourfoulad, M. (2012). Interaction of calf thymus DNA with the antiviral drug lamivudine. DNA and Cell Biology, 31(1), 122–127.

    Article  CAS  PubMed  Google Scholar 

  36. Ghalandari, B., Divsalar, A., Eslami-Moghadam, M., Saboury, A. A., Haertlé, T., Amanlou, M., & Parivar, K. (2015). Probing of the interaction between β-lactoglobulin and the anticancer drug oxaliplatin. Applied Biochemistry and Biotechnology, 175(2), 974–987.

    Article  CAS  PubMed  Google Scholar 

  37. Mostafavinia, S. E., & Hoshyar, R. (2016). Spectroscopic studies on the interaction of anticancer rosemary with ctDNA. Gene, Cell and Tissue, 3(2), e35638.

    Article  Google Scholar 

  38. Lang, P. T., Brozell, S. R., Mukherjee, S., Pettersen, E. F., Meng, E. C., Thomas, V., Rizzo, R. C., Case, D. A., James, T. L., & Kuntz, I. D. (2009). DOCK 6: combining techniques to model RNA–small molecule complexes. RNA, 15(6), 1219–1230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Arjmand, F., Parveen, S., Afzal, M., & Shahid, M. (2012). Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper (II) benzimidazole complexes. Journal of Photochemistry and Photobiology B: Biology, 114, 15–26.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The Research Council of Chemistry & Chemical Engineering Research Center of Iran is gratefully acknowledged for supporting this work.

Author information

Authors and Affiliations

  1. Department of Chemistry, Science and Research branch, Islamic Azad University, Tehran, Iran

    Fatemeh Safa Shams Abyaneh & Moyaed Hosaini Sadr

  2. Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran

    Mahboube Eslami Moghadam

  3. Department of Cell & Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Adeleh Divsalar

  4. School of Chemistry, Damghan University, Damghan, Iran

    Davood Ajloo

Authors
  1. Fatemeh Safa Shams Abyaneh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mahboube Eslami Moghadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adeleh Divsalar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Davood Ajloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Moyaed Hosaini Sadr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mahboube Eslami Moghadam.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shams Abyaneh, F.S., Eslami Moghadam, M., Divsalar, A. et al. Improving of Anticancer Activity and Solubility of Cisplatin by Methylglycine and Methyl Amine Ligands Against Human Breast Adenocarcinoma Cell Line. Appl Biochem Biotechnol 186, 271–291 (2018). https://doi.org/10.1007/s12010-018-2715-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-018-2715-5

Keywords

Search

Navigation