Skip to main content
SpringerLink
Log in

Computer simulation of the binding of amonafide and azonafide to DNA

  • Research Paper
  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Summary

Intercalative binding of the antitumor drugs amonafide and azonafide to the oligonucleotide duplex d(GGCCGGCCGG)·d(CCGGCCGGCC) was compared using molecular dynamics in vacuum with the AMBER force field. A number of reasonable possible binding conformations were obtained, with the azonafide complexes favored over the amonafide complexes in net binding enthalpy. In comparison with amonafide, the larger chromophore of azonafide permits greater DNA distortion and wider side-chain swings, without falling out of the intercalation site. The best model obtained was used for further dynamics on amonafide and azonafide with solvent and counterions present, and again the azonafide complex had a more favorable enthalpy. Furthermore, the enthalpy change on going from solvent into the intercalation site was less unfavorable for azonafide. These results are consistent with the stronger DNA binding of azonafide compared to amonafide, as observed in relative melting transition temperature increases and tumor inhibition in cell cultures.

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. Braña, M.F., Sanz, A.M., Castellano, J.M., Roldan, C.M. and Roldan, C., Eur. J. Med. Chem., 16 (1981) 207.

    Google Scholar 

  2. Braña, M.F., Castellano, J.M., Roldan, C.M., Santos, A., Vasquez, D. and Jimenez, A., Cancer Chemother. Pharmacol., 4 (1980) 61.

    PubMed  Google Scholar 

  3. Weiss, G.R., Burris III, H.A., Eckardt, J.R., Fields, S., O'Rourke, T., Rodriguez, G.I. and Rothenberg, M.L., Cancer Chemother. Biol. Response Modifiers Annu., 15 (1994) 130.

    Google Scholar 

  4. Saez, R., Craig, J., Weiss, G., Havlin, K., Hardy, J., Clark, G., Kuhn, J., Koeller, J. and Von Hoff, D., Proc. ASCO, 7 (1988) 59.

    Google Scholar 

  5. Llombart, M., Poveda, A., Forner, E., Fernandez-Martos, C., Gaspar, C., Munoz, M., Olmos, T., Ruiz, A., Soriano, V., Benavides, A., Martin, M., Schlick, E. and Guillem, V., Invest. New Drugs, 10 (1992) 177.

    PubMed  Google Scholar 

  6. Allen, S.L., Ratain, M., Korzun, A.H., Duggan, D., Novak, A., Norton, L. and Henderson, I.C., Proc. Am. Assoc. Cancer Res., 32 (1991) 183.

    Google Scholar 

  7. Waring, M.J., Gonzalez, A., Jiminez, A. and Vasquez, D., Nucleic Acids Res., 7 (1979) 217.

    PubMed  Google Scholar 

  8. Anderson, B.S., Beran, M., Bakic, M., Silberman, L.E., Newman, R.A. and Zwelling, L.A., Cancer Res., 47 (1987) 1040.

    PubMed  Google Scholar 

  9. Sami, S.M., Dorr, R.T., Alberts, D.S. and Remers, W.A., J. Med. Chem., 36 (1993) 765.

    PubMed  Google Scholar 

  10. Dorr, R.T., Remers, W.A., Alberts, D.S., Salmon, S.E. and Hersh, E.M., Proc. Am. Assoc. Cancer Res., 34 (1994) 39.

    Google Scholar 

  11. Sami, S.M., Dorr, R.T., Sólyom, A.M., Alberts, D.S. and Remers, W.A., J. Med. Chem., 38 (1995) 983.

    PubMed  Google Scholar 

  12. Feigon, J., Denny, W.A., Leupin, W.W. and Kearns, D.R., J. Med. Chem., 27 (1984) 450.

    PubMed  Google Scholar 

  13. Neidle, S., Drugs Exp. Clin. Res., 12 (1986) 455.

    PubMed  Google Scholar 

  14. Hingerty, B.E., Figuerou, S., Hayden, T.L. and Broyde, S., Biopolymers, 28 (1989) 1195.

    PubMed  Google Scholar 

  15. Taylor, E.R. and Olson, W.K., Biopolymers, 22 (1983) 2667.

    PubMed  Google Scholar 

  16. Manning, G.S., Q. Rev. Biophys., 11 (1978) 179.

    PubMed  Google Scholar 

  17. Barkley, M.D., Thomas, T.J., Maskos, K. and Remers, W.A., Biochemistry, 30 (1991) 4421.

    PubMed  Google Scholar 

  18. Pearlstein, R.A., Chemlab-II Reference Manual, Molecular Design Ltd., San Leandro, CA, 1985.

    Google Scholar 

  19. Singh, U.C., Weiner, P.L., Caldwell, J. and Kollman, P.A., AMBER 3.0 and QUEST 1.0 Documentation, University of California, San Francisco, CA, 1986.

    Google Scholar 

  20. Weiner, S.J., Kollman, P.A., Case, D., Singh, U.C., Ghio, C., Alagona, G., Profeta, S. and Weiner, P.K., J. Am. Chem. Soc., 106 (1984) 765.

    PubMed  Google Scholar 

  21. Ferrin, T.E., Huang, C.C., Jarvis, L.E. and Langridge, R., J. Mol. Graphics, 6 (1988) 1.

    Google Scholar 

  22. Ferrin, T.E., Huang, C.C., Jarvis, L.E. and Langridge, R., J. Mol. Graphics, 6 (1988) 13.

    Google Scholar 

  23. Jorgensen, W., Chandrasekhar, T. and Madura, T., J. Chem. Phys., 79 (1983) 926.

    Article  Google Scholar 

  24. Pearlman, D.A., Case, D.A., Caldwell, J.C., Seibel, G.L., Singh, U.C., Weiner, P. and Kollman, P.A., AMBER 4.0 Documentation, University of California, San Francisco, CA, 1991.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 85721, Tucson, AZ, USA

    Soaring Bear & William A. Remers

Authors
  1. Soaring Bear
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William A. Remers
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bear, S., Remers, W.A. Computer simulation of the binding of amonafide and azonafide to DNA. J Computer-Aided Mol Des 10, 165–175 (1996). https://doi.org/10.1007/BF00402824

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00402824

Keywords

Search

Navigation