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Moreover, many fatty acids and derivatives, including the broad-spectrum antiseizure medication valproic acid, have been explored and used as pharmacological agents to treat epilepsy. In this work, we have explored the anticonvulsant potential of a large library of fatty acids and fatty acid derivatives, the LIPID MAPS Structure Database, using structure-based virtual screening to assess their ability to block the voltage-gated sodium channel 1.2 (NaV1.2), a validated target for antiseizure medications. Four of the resulting in silico hits were submitted for experimental confirmation using in vitro patch clamp experiments, and their protective role was evaluated in an acute mice seizure model, the Maximal Electroshock seizure model. These four compounds were found to protect mice against seizures. Two of them exhibited blocking effects on NaV1.2, CaV2.2, and CaV3.1.<\/jats:p>","DOI":"10.3390\/pharmaceutics16080996","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T15:26:53Z","timestamp":1722526013000},"page":"996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Silico Screening Identification of Fatty Acids and Fatty Acid Derivatives with Antiseizure Activity: In Vitro and In Vivo Validation"],"prefix":"10.3390","volume":"16","author":[{"given":"Emilia Mercedes","family":"Barrionuevo","sequence":"first","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Peralta","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4968-1962","authenticated-orcid":false,"given":"Agust\u00edn","family":"Manzur De Nardi","sequence":"additional","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos (IIFP), Universidad Nacional de La Plata\u2013CICPBA\u2013CONICET, Boulevard 120 no. 1489, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0607-6681","authenticated-orcid":false,"given":"Juliana","family":"Monat","sequence":"additional","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos (IIFP), Universidad Nacional de La Plata\u2013CICPBA\u2013CONICET, Boulevard 120 no. 1489, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano Jos\u00e9","family":"Fallico","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel Augusto","family":"Llanos","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-3788","authenticated-orcid":false,"given":"Luciana","family":"Gavernet","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio Rom\u00e1n","family":"Mustaf\u00e1","sequence":"additional","affiliation":[{"name":"Electrophysiology Laboratory of the Multidisciplinary Institute of Cell Biology [Argentine Research Council (CONICET), Scientific Research Commission of the Province of Buenos Aires (CIC-PBA) and National University of La Plata (UNLP)], La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Martin","sequence":"additional","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos (IIFP), Universidad Nacional de La Plata\u2013CICPBA\u2013CONICET, Boulevard 120 no. 1489, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Talevi","sequence":"additional","affiliation":[{"name":"Laboratory of Bioactive Compound Research and Development (LIDeB), Faculty of Exact Sciences, National University of La Plata (UNLP), Blvd. 120 1489, La Plata 1900, Argentina"},{"name":"Argentinean National Council of Scientific and Technical Research (CONICET), CCT La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Diseases and Injuries Collaborators (2020). 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