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

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Abstract

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Department of Chemistry, Faculty of Exact Sciences, Universidad Nacional de La Plata, B1900AVV, La Plata, Buenos Aires, Argentina

    Alan Talevi & Eduardo A. Castro

  2. Department of Biological Sciences, Faculty of Exact Sciences, Universidad Nacional de La Plata, 47 y 115, B1900AVV, La Plata, Buenos Aires, Argentina

    Alan Talevi, Carolina L. Bellera & Luis E. Bruno-Blanch

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  1. Alan Talevi
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  2. Carolina L. Bellera
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  3. Eduardo A. Castro
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  4. Luis E. Bruno-Blanch
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Correspondence to Luis E. Bruno-Blanch.

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Talevi, A., Bellera, C.L., Castro, E.A. et al. A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben. J Comput Aided Mol Des 21, 527–538 (2007). https://doi.org/10.1007/s10822-007-9136-9

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  • DOI: https://doi.org/10.1007/s10822-007-9136-9

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