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Exploration of the Binding Mode of Indole Derivatives as Potent HIV-1 Inhibitors Using Molecular Docking Simulations

  • Balupuri, Anand (Departments of Bio-New Drug Development, Chosun University) ;
  • Cho, Seung Joo (Departments of Bio-New Drug Development, Chosun University)
  • Received : 2013.09.04
  • Accepted : 2013.09.23
  • Published : 2013.09.30

Abstract

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

Keywords

References

  1. W. S. Blair, P. F. Lin, N. A. Meanwell, and O. B. Wallace, "HIV-1 entry-an expanding portal for drug discovery", Drug Discov. Today, Vol. 5, pp. 183-194, 2000. https://doi.org/10.1016/S1359-6446(00)01484-7
  2. Q. Guo, H. T. Ho, I. Dicker, L. Fan, N. Zhou, J. Friborg, T. Wang, B. V. McAuliffe, H. G. Wang, R. E. Rose, H. Fang, H. T. Scarnati, D. R. Langley, N. A. Meanwell, R. Abraham, R. J. Colonno, and P. F. Lin, "Biochemical and genetic characterizations of a novel human immunodeficiency virus type 1 inhibitor that blocks gp120-CD4 interactions", J. Virol., Vol. 77, pp. 10528-10536, 2003. https://doi.org/10.1128/JVI.77.19.10528-10536.2003
  3. J. P. Moore and R. W. Doms, "The entry of entry inhibitors: a fusion of science and medicine", Proc. Natl. Acad. Sci. USA, Vol. 100, pp. 10598-10602, 2003. https://doi.org/10.1073/pnas.1932511100
  4. E. A. Berger, P. M. Murphy, and J. M. Farber, "Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease", Annu. Rev. Immunol., Vol. 17, pp. 657-700, 1999. https://doi.org/10.1146/annurev.immunol.17.1.657
  5. K. S. Yeung, Z. Qiu, Q. Xue, H. Fang, Z. Yang, L. Zadjura, C. J. D'Arienzo, B. J. Eggers, K. Riccardi, P. Y. Shi, Y. F. Gong, M. R. Browning, Q. Gao, S. Hansel, K. Santone, P. F. Lin, N. A. Meanwell, and J. F. Kadow, "Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents", Bioorg. Med. Chem. Lett., Vol. 23, pp. 198-202, 2013. https://doi.org/10.1016/j.bmcl.2012.10.115
  6. K. S. Yeung, Z. Qiu, Z. Yin, A. Trehan, H. Fang, B. Pearce, Z. Yang, L. Zadjura, C. J. D'Arienzo, K. Riccardi, P. Y. Shi, T. P. Spicer, Y. F. Gong, M. R. Browning, S. Hansel, K. Santone, J. Barker, T. Coulter, P. F. Lin, N. A. Meanwell, and J. F. Kadow, "Inhibitors of HIV-1 attachment. Part 8: the effect of C7-heteroaryl substitution on the potency, and in vitro and in vivo profiles of indole-based inhibitors", Bioorg. Med. Chem. Lett., Vol. 23, pp. 203-208, 2013. https://doi.org/10.1016/j.bmcl.2012.10.117
  7. K. S. Yeung, Z. Qiu, Z. Yang, L. Zadjura, C. J. D'Arienzo, M. R. Browning, S. Hansel, X. S. Huang, B. J. Eggers, K. Riccardi, P. F. Lin, N. A. Meanwell, and J. F. Kadow, "Inhibitors of HIV-1 attachment. Part 9: an assessment of oral prodrug approaches to improve the plasma exposure of a tetrazole- containing derivative", Bioorg. Med. Chem. Lett., Vol. 23, pp. 209-212, 2013. https://doi.org/10.1016/j.bmcl.2012.10.125
  8. C. G. Gadhe and S. J. Cho, "Modulation of multidrug resistance in cancer by P-glycoprotein", J. Chosun Natural Sci., Vol. 4, pp. 23-30, 2011.
  9. S. J. Cho, "Recent development of search algorithm on small molecule docking", J. Chosun Natural Sci., Vol. 2, pp. 55-58, 2009.
  10. G. Kothandan, T. Madhavan, C. G. Gadhe, and S. J. Cho, "Pseudoreceptor: Concept and an overview", J. Chosun Natural Sci., Vol. 3, pp. 162-167, 2010.
  11. S. J. Cho, "Search space reduction techniques in small molecular docking", J. Chosun Natural Sci., Vol. 3, pp. 143-147, 2010.
  12. S. J. Cho, "Calculation and application of partial charges", J. Chosun Natural Sci., Vol. 3, pp. 226-230, 2010.
  13. G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, and A. J. Olson, "AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility", J. Comput. Chem., Vol. 30, pp. 2785-2791, 2009. https://doi.org/10.1002/jcc.21256
  14. S. H. Xiang, P. D. Kwong, R. Gupta, C. D. Rizzuto, D. J. Casper, R. Wyatt, L. Wang, W.A. Hendrickson, M. L. Doyle, and J. Sodroski, "Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein", J. Virol., Vol. 76, pp. 9888-9899, 2002. https://doi.org/10.1128/JVI.76.19.9888-9899.2002
  15. R. Kong, J. J. Tan, X. H. Ma, W. Z. Chen, and C. X. Wang, "Prediction of the binding mode between BMS-378806 and HIV-1 gp120 by docking and molecular dynamics simulation", Biochim. Biophys. Acta., Vol. 1764, pp. 766-772, 2006. https://doi.org/10.1016/j.bbapap.2005.12.017
  16. C. G. Gadhe, G. Kothandan, T. Madhavan, and S. J. Cho, "Molecular modeling study of HIV-1 gp120 attachment inhibitors", Med. Chem. Res., Vol. 21, pp. 1892-1904, 2012. https://doi.org/10.1007/s00044-011-9711-4

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