Virtual screening applied to the discovery of new anticonvulsant drugs for the treatment of refractory epilepsy

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

Congreso; XXXVIII Congreso de Quimicos Teoricos de Expresion Latina; 2012

We present in this investigation the results obtained from a sequential virtual screening campaign designed to find new anticonvulsant structures with no affinity to P-gp. To this end, we applied a 3-model ensemble of 2D QSAR classifiers capable of differentiating Pgp-substrates from non-substrates [3] in conjunction with a topological model capable of identifying anticonvulsants [4] to the Zinc [5] and DrugBank [5] databases. After that, 380 compounds were selected for a docking-based virtual screening. As the 3D structure of human P-gp is not available, a homology model was constructed based on the X-ray structure of the mouse P-gp (PDB code=360).