Journal of Computer-Aided Molecular Design

, Volume 21, Issue 9, pp 527–538 | Cite as

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben

  • Alan Talevi
  • Carolina L. Bellera
  • Eduardo A. Castro
  • Luis E. Bruno-BlanchEmail author


A discriminant function based on topological descriptors was derived from a training set composed by anticonvulsants of clinical use or in clinical phase of development and compounds with other therapeutic uses. This model was internally and externally validated and applied in the virtual screening of chemical compounds from the Merck Index 13th. Methylparaben (Nipagin), a preservative widely used in food, cosmetics and pharmaceutics, was signaled as active by the discriminant function and tested in mice in the Maximal Electroshock (MES) test (i.p. administration), according to the NIH Program for Anticonvulsant Drug Development. Based on the results of Methylparaben, Propylparaben (Nipasol), another preservative usually used in association with the former, was also tested. Both methyl and propylparaben were found active in mice at doses of 30, 100, and 300 mg/kg. The discovery of the anticonvulsant activities in the MES test of methylparaben and propylparaben might be useful for the development of new anticonvulsant medications, specially considering the well-known toxicological profile of these drugs.


Virtual Screening Anticonvulsants MES Methylparaben Propylparaben 



We want to thank Guillermina Estiú (University of Notre Dame) and Luciana Gavernet for their valuable help in bibliographic search and Rubén Greco for his valuable assistance in biological tests. A. Talevi thanks CONICET for his Type I Post grade Fellowship. E.A. Castro is a member of CONICET. L.E. Bruno-Blanch thanks the Facultad de Ciencias Exactas de la Universidad Nacional de La Plata (Incentivos UNLP) and the Agencia Nacional de Promoción Científica y Tecnológica (PICT BIB 1728/06-11985).


  1. 1.
    Frank RG (2003) J Health Econ 22:325CrossRefGoogle Scholar
  2. 2.
    DiMasi JA, Hansen RW, Grabowski HG, (2003) J Health Econ 22:151CrossRefGoogle Scholar
  3. 3.
    Dickson M, Gagnon JP (2004) Discov Med 4:172Google Scholar
  4. 4.
    Willett P (2006) Drug Discov Today 11:1046CrossRefGoogle Scholar
  5. 5.
    Comission on Epidemiology, Prognosis, International League Against Epilepsy (1993) Epilepsia 34:592Google Scholar
  6. 6.
    Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, Engel J Jr (2005) Epilepsia 46:470CrossRefGoogle Scholar
  7. 7.
    World Health Organization (2001) Fact sheet no. 165: Aetiogy, epidemiology and prognosisGoogle Scholar
  8. 8.
    World Health Organization (2001) Fact sheet no. 265: Mental and neurological disordersGoogle Scholar
  9. 9.
    Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Loiseau P, Perucca E (2002) Epilepsy Res 51:31CrossRefGoogle Scholar
  10. 10.
    Mahmoudi N; de Julián-Ortiz JV, Ciceron L, Gálvez J., Mazier D, Danis M, Derouin F, García-Domenech R (2006) J Antimicrob Chemother 75:489CrossRefGoogle Scholar
  11. 11.
    García-García A, Gálvez J, de Julián-Ortiz JV, García-Domenech R, Muñoz C, Guna1 R, Borrás R (2004) J Antimicrob Chemother 53:65CrossRefGoogle Scholar
  12. 12.
    Marrero-Ponce Y, Machado Tugores Y, Pereira DN, Escario JA, Barrio AG, Nogal-Ruiz JJ, Ochoa C, Aran VJ, Martínez-Fernández AR, García-Sánchez RN, Montero-Torres A, Torrens F, Meneses-Marcel A (2005) Curr Drug Discov Technol 2:245CrossRefGoogle Scholar
  13. 13.
    Montero-Torres A, García-Sánchez RM, Machado-Tugores Y, Nogal-Ruiz JJ, Martínez-Fernández AR, Aran VJ, Ochoa C, Meneses-Marcel A, Torrens F (2006) Eur J Med Chem 41:483CrossRefGoogle Scholar
  14. 14.
    Prieto JJ, Talevi A, Bruno-Blanch LE (2006) Mol Divers 10:361CrossRefGoogle Scholar
  15. 15.
    Talevi A, Bellera CL, Castro EA, Bruno-Blanch LE (2006) Drugs Future 31(Suppl. A):XIXth Int Symp Med Chem, p 188Google Scholar
  16. 16.
    Talevi A, Sella-Cravero M, Castro EA, Bruno-Blanch LE (2007) Bioorg Med Chem Lett 17:1684CrossRefGoogle Scholar
  17. 17.
    Soni MG, Taylor SL, Greenberg NA, Burdock GA (2002) Food Chem Toxicol 40:1335CrossRefGoogle Scholar
  18. 18.
    Soni MG, Burdock GA, Taylor SL, Greenberg NA (2001) Food Chem Toxicol 39:513CrossRefGoogle Scholar
  19. 19.
    Talete srl DRAGON for Windows (Software for Molecular Descriptors Calculation) (2003) Version 4.0,
  20. 20.
    National Institute of Statistical Sciences. PowerMV Version 0.61,
  21. 21.
    Statsoft, Inc. STATISTICA (1996) Version 5.1,
  22. 22.
    Yasri A, Hartsough D (2001) J Chem Inf Comput Sci 41:1218CrossRefGoogle Scholar
  23. 23.
    Obniska J, Kaminski K, Zagorska A, Dzierzawska-Majewska A, Karolak-Wojciechowska J (2006) J Fluorine Chem 127:417CrossRefGoogle Scholar
  24. 24.
    Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Loiseau P, Perucca E (1999) Epilepsy Res 34:1CrossRefGoogle Scholar
  25. 25.
    De Sarro G, Ferreri G, Gareri P, Russo E, De Sarro A, Gitto R, Chimirri A (2003) Pharmacol Biochem Behav 74:595CrossRefGoogle Scholar
  26. 26.
    Ferreri G, Chimirri A, Russo E, Gitto R, Gareri P, De Sarro A, De Sarro G (2004) Pharmacol Biochem Behav 77:85CrossRefGoogle Scholar
  27. 27.
    Obniska J, Jurczyk S, Zejc A, Kaminski K, Tatarczynska E, Stachowicz K (2005) Pharmacol Rep 57:170Google Scholar
  28. 28.
    Schenck HA, Lenkowski PW, Choudhury-Mukherjee I, Ko S, Stables JP, Patel MK, Brown ML (2004) Bioorg Med Chem 12:979CrossRefGoogle Scholar
  29. 29.
    Beguin C, LeTiran A, Stables JP, Voyksner RD, Kohn H (2004) Bioorg Med Chem 12:3079CrossRefGoogle Scholar
  30. 30.
    Kaymakçıoğlu B, Rollas S, Körceğez E, Arıcıoğlu F (2005) Eur J Pharm Sci 26:97CrossRefGoogle Scholar
  31. 31.
    Gálvez J, García-Domenech C, de Alapont G, de Julián-Ortiz JV, Popa L (1996) J Mol Graph 14:272CrossRefGoogle Scholar
  32. 32.
    The Merck Index (2001) Encyclopedia of chemicals, drugs and biologicals, 13th edn. Merck and Co. Withehouse Station, New JerseyGoogle Scholar
  33. 33.
    Stables JP, Kupferberg HJ, Gladding R (1997) In: Avanzini G, Regesta G, Tanganelli P, Avoli M (eds) Molecular and cellular targets for antiepileptic drugs, John Libbey & Company Ltd., London, England, pp 191–198Google Scholar
  34. 34.
    Raychaudhury C, Ray SK, Ghosh JJ, Roy AB, Basak SC (1984) J Comput Chem 5:581CrossRefGoogle Scholar
  35. 35.
    Magnuson DR, Harris VK, Basak SC (1983) In: King RB (ed) Studies in physical and theoretical chemistry. Elsevier, Amsterdam, Netherlands, pp 178–191Google Scholar
  36. 36.
    Geary RC (1954) Incorp Stat 5:115CrossRefGoogle Scholar
  37. 37.
    Basak SC (1999) In: Devillers J, Balaban AT (eds) Topological indices and related descriptors in QSAR and QSPR. Gordon and Breach Science Publishers, Amsterdam, pp 563–593Google Scholar
  38. 38.
    Srivasta AK, Gupta YK (2001) Indian J Physiol Pharmacol 45:475Google Scholar
  39. 39.
    Walil RS, Patil PA (1995) Indian J Physiol Pharmacol 39:77Google Scholar
  40. 40.
    Bubnoff MV, Schnell D, Vogt-Mycoff J (1957) Arzeimittel Forschung 7:340Google Scholar
  41. 41.
    SciFinder Chemical Abstracts Service (American Chemical Society) (2006) Bibliographic database.
  42. 42.
    Levy RH, Dreifuss FE, Mattson RH, Meldrum BS, Kiffin Penry J (1989) Antiepileptic drugs. Raven Press, New YorkGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Alan Talevi
    • 1
    • 2
  • Carolina L. Bellera
    • 2
  • Eduardo A. Castro
    • 1
  • Luis E. Bruno-Blanch
    • 2
    Email author
  1. 1.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Department of Chemistry, Faculty of Exact SciencesUniversidad Nacional de La PlataLa Plata, Buenos AiresArgentina
  2. 2.Department of Biological Sciences, Faculty of Exact SciencesUniversidad Nacional de La PlataLa Plata, Buenos AiresArgentina

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