title: Several new diverse anticonvulsant agents discovered in a virtual screening campaign aimed at novel antiepileptic drugs to treat refractory epilepsy.
abstract: 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-glycoprotein 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.
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 & 115, La Plata B1900AJI, Buenos Aires, Argentina.
authors.forename: Mauricio E
authors.initials: ME
authors.lastname: Di Ianni
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Enrique
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Palestro
authors.forename: Luciana
authors.initials: L
authors.lastname: Gavernet
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno-Blanch
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D011487:Protein Conformation; D017211:Treatment Failure; D014584:User-Computer Interface
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants