title: A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben.
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.
authors.affiliation: 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.
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Bellera
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Castro
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno-Blanch
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data*; D003198:Computer Simulation; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D005520:Food Preservatives / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010226:Parabens / Q000737:chemistry / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
chemical_list: D000927:Anticonvulsants; D005520:Food Preservatives; D010226:Parabens; D011310:Preservatives, Pharmaceutical; C015358:methylparaben; C006068:propylparaben