Skip to main content
SpringerLink
Log in

Novel imidazolyl derivatives of 1,8-acridinedione as potential DNA-intercalating agents

  • Published:
Journal of the Iranian Chemical Society Aims and scope Submit manuscript

Abstract

The effect of twelve novel imidazolyl derivatives of 1,8-acridinedione (ligands) on calf thymus DNA was studied applying different biophysical techniques including UV-Vis spectrophotometry, CD spectropolarimetry and fluorimetric methods to gain deeper insights into the mechanism of interaction of the ligands with DNA. The binding parameters such as C50, K app, ΔGo (H2O) and m-value, followed by Scatchard analysis, indicate that among the tested ligands, four compounds; 12b, 13b, 12f and 13f, containing nitro and benzyl imidazole substituents, revealed uncompetitive intercalative mode of interaction with DNA. UV-Vis studies imply that the compounds bind cooperatively to DNA at the concentration range of 100-200 μM. Based on biophysical data, QSAR analysis, and docking simulations, we propose that in cytotoxic 1,8-acridinediones, the imidazole moiety is essential for pharmacological activity and the introduction of more flexible and electron-withdrawing substituents on the imidazole ring serves to enhance their DNA intercalating ability.

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

Similar content being viewed by others

References

  1. S. Catoen-Chackal, M. Facompre, R. Houssin, N. Pommery, J.F. Goossens, P.C. Bailly, J.P. Hénichart, J. Med. Chem. 47 (2004) 3665.

    CAS  Google Scholar 

  2. R. Martinez, L. Chacon-Garcia, Current Med. Chem. 12 (2005) 127.

    CAS  Google Scholar 

  3. A.A. Adjei, Invest. New Drugs. 17 (1999) 43.

    CAS  Google Scholar 

  4. J. Konopa, Pure Appl. Chem. 73 (2001) 1421.

    CAS  Google Scholar 

  5. J. Mazerski, K. Muchewicz, Acta Biochimica Polonica 47 (2000) 65.

    CAS  Google Scholar 

  6. P. Belmont, I. Dorange, Expert Opin. Ther. Patents 18 (2008) 1211.

    CAS  Google Scholar 

  7. K. Palani, P. Ambalavanan, M.N. Ponnuswamy, P. Murugan, V.T. Ramakrishnan, Cryst. Res. 40 (2005) 277.

    CAS  Google Scholar 

  8. S.J. Tu Qian Wang, J.P. Zhang, X.T. Zhu, J.N. Xu, Acta Cryst. E61 (2005) 3743.

    Google Scholar 

  9. J. Jeyakanthan, M. Yogavel, T. Joseph Rajan, D. Velmurugan, K. Sekar, Cryst. Res. Technol. 37 (2002) 1029.

    CAS  Google Scholar 

  10. G. Murali, T.R. Miller, S.A. Buckner, I. Milicic, E.J. Molinari, L.K. Whitecker, R. Davis-Taber, V. E. Scott, C. Cassidy, J.P. Sullivan, W.A. Carroll, Brit. J. Pharmacol. 138 (2003) 393.

    Google Scholar 

  11. M.G. Gunduz, A.E. Dogan, R. Simsek, K. Erol, C. Safak, Med. Chem. Res. 18 (2009) 317.

    Google Scholar 

  12. S.A. Pandi, D. Velmurugan, M.M. Govind, M.J. Kim, T. Josephrajan, Cryst. Res. Technol. 37 (2002) 293.

    Google Scholar 

  13. K. Palani, D. Thirumalai, P. Ambalavanan, M.N. Ponnuswamy, V.T. Ramakrishnan, J. Chem. Cryst. 35 (2005) 751.

    CAS  Google Scholar 

  14. P. Murugan, K.C. Hwang, V.T. Ramakrishnan, S. Balasubramanian, J. Materials Online 1 (2005) 1.

    Google Scholar 

  15. W.D. McFadyen, N. Sotirellis, W.A. Denny, P.G. Wakelin, Biochem. Biophys. Acta 1084 (1990) 50.

    Google Scholar 

  16. A. Jamalian, R. Miri, O. Firuzi, M. Amini, A.A. Moosavi Movahedi, A. Shafiee, J. Iran. Chem. Soc. 8 (2011) 983.

    CAS  Google Scholar 

  17. S.Z. Bathaie, A.A. Moosavi-Movahedi, A.A. Saboury, Nucleic Acids Res. 27 (1999) 1001.

    CAS  Google Scholar 

  18. A.A. Saboury, J. Iran. Chem. Soc. 3 (2006) 1.

    Article  CAS  Google Scholar 

  19. A.A. Saboury, A.A. Moosavi-Movahedi, H. Mansouri-Torshizi, J. Chin. Chem. Soc. 46 (1999) 917.

    CAS  Google Scholar 

  20. R.F. Greene, C.N. Pace, J. Biol. Chem. 249 (1974) 5388.

    CAS  Google Scholar 

  21. K.G. Strothkamp, R.E. Strothkamp, J. Chem. Edu. 71 (1994) 77.

    CAS  Google Scholar 

  22. A.J. Geall, I.S. Blagbrough, J. Pharmaceut. Biomed. Anal. 22 (2000) 849.

    CAS  Google Scholar 

  23. M. Howe-Grant, K.C. Wu, W.R. Bauet, S. Lippard, J. Biochem. 17 (1976) 1251.

    Google Scholar 

  24. H. Mansouri-Torshizi, M. Moghaddam, A. Divsalar, A.A. Saboury, Bioorg. Med. Chem. 16 (2008) 9616.

    CAS  Google Scholar 

  25. L. Fenghua, Z. Guanghua, W. Hongxing, Z. Shourong, L. Huakuan, Trans. Metal Chem. 31 (2006) 630

    Google Scholar 

  26. Y. Li, Z. Yang, T. Li, Z. Liu, B. Wang, J. Fluoresc 20 (2010) 891.

    Google Scholar 

  27. A.G. Krishna, D.V. Kumar, B.M. Khan, S.K. Rawal, K.N. Ganesh, Biochim. Biophys. Acta 1381 (1998) 104.

    CAS  Google Scholar 

  28. L. Peres-Flores, A.J. Ruiz-Chica, J.G. Delcros, F.M. Sanches, F.J. Ramirez, Spectrochim. Acta Part A 69 (2008) 1089.

    Google Scholar 

  29. M. Islami-Moghaddam, H. Mansouri-Torshizia, A. Divsalarb, A.A. Saboury, J. Iran. Chem. Soc. 6 (2009) 552.

    Article  CAS  Google Scholar 

  30. G.M. Morris, D.S. Goodsell, R.S. Halliday, R. Huey, W.E. Hart, R.K. Belew, A.J. Olson, J. Comput. Chem. 19 (1998) 1639.

    CAS  Google Scholar 

  31. L.D. Frederick, G. Williams, G.A. Ughetto, J.H. Van der Marel, R. Van Boom, H.J. Wang, Biochemistry 29 (1990) 2538.

    CAS  Google Scholar 

  32. A. Madadkar-Sobhani, S. Rasoul amini, J.D.A. Tyndall, E. Azizi, M. Daneshtalab, A. Khalaj, J. Mol. Graph. Model. 25 (2006) 459.

    Google Scholar 

  33. M.J. Frisch, M.J. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery, J.R. Stratmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels, K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski, J.V. Ortiz, A.G. Baboul, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, J.L. Andres, C. Gonzalez, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian 98, Revision A.7, Pittsburgh PA Inc., Penncylvania, 1998.

    Google Scholar 

  34. M. Khoshneviszadeh, N. Edraki, R. Miri, B. Hemmateenejad, Chem. Biol. Drug Des. 72 (2008) 564.

    CAS  Google Scholar 

  35. R. Miri, K. Javidnia, H. Mirkhani, B. Hemmateenejad, Z. Sepehr, M. Zalpour, T. Behzad, M. Khoshneviszadeh, N.A.R. Edraki, Mehdipour, Chem. Biol. Drug Des. 70 (2007) 329.

    CAS  Google Scholar 

  36. N. Edraki, B. Hemmateenejad, R. Miri, M. Khoshneviszadeh, Chem. Biol. Drug Des. 70 (2007) 530.

    CAS  Google Scholar 

  37. A.A. Moosavi Movahedi, B. Samiee, G.H. Hakimelahi, J. Colloid Interface Sci. 161 (1993) 53.

    Google Scholar 

  38. C.N. Pace, TIB Tech. 8 (1990) 93.

    CAS  Google Scholar 

  39. R.J. Fiel, J. Biol. Struct. Dyn. 6 (1989) 1259.

    CAS  Google Scholar 

  40. A. Rajendran, B. Unni Nair, Biochim. Biophys. Acta 1760 (2006) 1794.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    A. Jamalian, A. Shafiee & M. Khoshneviszadeh

  2. Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    A. Shafiee

  3. Medicinal and Natural Product Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    B. Hemmateenejad & R. Miri

  4. Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    R. Miri

  5. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    A. Madadkar-Sobhani & A. A. Moosavi-Movahedi

  6. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    S. Z. Bathaie

  7. Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran

    A. A. Moosavi-Movahedi

Authors
  1. A. Jamalian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Shafiee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Hemmateenejad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Khoshneviszadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Miri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Madadkar-Sobhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Z. Bathaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A. A. Moosavi-Movahedi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. A. Moosavi-Movahedi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jamalian, A., Shafiee, A., Hemmateenejad, B. et al. Novel imidazolyl derivatives of 1,8-acridinedione as potential DNA-intercalating agents. JICS 8, 1098–1112 (2011). https://doi.org/10.1007/BF03246568

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03246568

Key words

Search

Navigation