Doklady Biochemistry and Biophysics

, Volume 470, Issue 1, pp 371–374 | Cite as

Prediction of blood-brain barrier permeability of organic compounds

  • A. S. Dyabina
  • E. V. Radchenko
  • V. A. Palyulin
  • N. S. Zefirov
Biochemistry, Biophysics, and Molecular Biology

Abstract

Using fragmental descriptors and artificial neural networks, a predictive model of the relationship between the structure of organic compounds and their blood-brain barrier permeability was constructed and the structural factors affecting the readiness of this penetration were analyzed. This model (N = 529, Q 2 = 0.82, RMSE cv = 0.32) surpasses the previously published models in terms of the prediction accuracy and the applicability domain and can be used for the optimization of the pharmacokinetic parameters during drug development.

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References

  1. 1.
    Di, L., Rong, H., and Feng, B., J. Med. Chem., 2013, vol. 56, no. 1, pp. 2–12.CrossRefPubMedGoogle Scholar
  2. 2.
    Wager, T.T., Liras, J.L., Mente, S., and Trapa, P., Expert Opin. Drug Metab. Toxicol., 2012, vol. 8, no. 5, pp. 531–542.CrossRefPubMedGoogle Scholar
  3. 3.
    Garg, P., Verma, J., and Roy, N., In silico modeling for blood-brain barrier permeability predictions, in Drug Absorption Studies, New York: Springer, 2008, pp. 510–556.Google Scholar
  4. 4.
    Lanevskij, K., Japertas, P., and Didziapetris, R., Expert Opin. Drug Metab. Toxicol., 2013, vol. 9, no. 4, pp. 473–486.CrossRefPubMedGoogle Scholar
  5. 5.
    Palyulin, V.A., Dyabina, A.S., Radchenko, E.V., and Zefirov, N.S., in ISMC EFMC XXII Intern. Symp. on Medicinal Chemistry, Berlin, September 2–6, 2012, Berlin, 2012, pp. 374–375.Google Scholar
  6. 6.
    Instant JChem 16.4.11, ChemAxon Ltd., 2016. http://www.chemaxon.com.Google Scholar
  7. 7.
    Baskin I.I., Halberstam N.M., Artemenko N.V., Palyulin V.A., Zefirov N.S., in: EuroQSAR 2002 Designing Drugs and Crop Protectants: Processes, Problems and Solutions, Oxford: Blackwell, 2003, pp. 260–263.Google Scholar
  8. 8.
    Artemenko, N.V., Baskin, I.I., Palyulin, V.A., and Zefirov, N.S., Russ. Chem. Bull., 2003, vol. 52, no. 1, pp. 20–29. Izv. Akad. Nauk, Ser. Khim., 2003, vol. 52, pp. 19–28.CrossRefGoogle Scholar
  9. 9.
    Zefirov, N.S. and Palyulin, V.A., J. Chem. Inf. Comput. Sci., 2002, vol. 42, no. 5, pp. 1112–1122.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhokhova, N.I., Baskin, I.I., Palyulin, V.A., Zefirov, A.N., and Zefirov, N.S., Dokl. Chem., 2007, vol. 417, no. 2, pp. 282–284.CrossRefGoogle Scholar
  11. 11.
    Muehlbacher, M., Spitzer, G.M., Liedl, K.R., and Kornhuber, J., J. Comput.-Aided Mol. Des., 2011, vol. 25, no. 12, pp. 1095–1106.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Clark, D.E., Drug Discov. Today, 2003, vol. 8, no. 20, pp. 927–933.CrossRefPubMedGoogle Scholar
  13. 13.
    Martins, I.F., Teixeira, A.L., Pinheiro, L., and Falcao, A.O., J. Chem. Inf. Mod., 2012, vol. 52, no. 6, pp. 1686–1697.CrossRefGoogle Scholar
  14. 14.
    Baskin, I.I., Ait, A.O., Halberstam, N.M., Palyulin, V.A., and Zefirov, N.S., SAR QSAR Environ. Res., 2002, vol. 13, no. 1, pp. 35–41.CrossRefPubMedGoogle Scholar
  15. 15.
    Radchenko, E.V., Karpov, P.V., Sosnin, S.B., Palyulin, V.A., and Zefirov, N.S., in XXII Ros. nats. kongress “Chelovek i lekarstvo,” Moskva, 6-10 aprelya 2015 (XXII Russ. Natl. Congr. “Man and Drug,” Moscow, April 6–10, 2015), Moscow, 2015, p. 250.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • A. S. Dyabina
    • 1
  • E. V. Radchenko
    • 1
    • 2
  • V. A. Palyulin
    • 1
    • 2
  • N. S. Zefirov
    • 1
    • 2
  1. 1.Department of ChemistryLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow oblastRussia

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