Several new diverse anticonvulsant agents discovered in a virtual screening campaign aimed at novel antiepileptic drugs to treat refractory epilepsy

DI IANNI MAURICIO; ENRIQUE ANDREA; PALESTRO PABLO; GAVERNET LUCIANA; TALEVI ALAN; BRUNO BLANCH LUIS E.

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Lugar: Washington; Año: 2012 p. 3325 - 3330

1549-9596

A virtual screening campaign was conducted in order to discover new anticonvulsant drug candidates for the treatment of refractory epilepsy. To this purpose, a topological discriminant function to identify antiMES drugs and a sequential filtering methodology to discriminate P-glycopro- tein substrates and nonsubstrates were jointly applied to ZINC 5 and DrugBank databases. The virtual filters combine an ensemble of 2D classifiers and docking simulations. In the light of the results, 10 structurally diverse compounds were acquired and tested in animal models of seizure and the rotorod test. All 10 candidates showed some level of protection against MES test.