Artículo
Design, synthesis and biological evaluation of N-substituted α-hydroxyimides and 1,2,3-oxathiazolidine-4-one-2,2-dioxides with anticonvulsant activity
Sabatier, Laureano Leonel
; Palestro, Pablo Hernán
; Enrique, Andrea Verónica
; Pastore, Valentina
; Sbaraglini, Maria Laura
; Martín, Pedro
; Gavernet, Luciana
Fecha de publicación:
14/08/2019
Editorial:
Taylor & Francis Ltd
Revista:
Journal of Enzyme Inhibition and Medicinal Chemistry
ISSN:
1475-6366
e-ISSN:
1475-6374
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
In this investigation, we studied a family of compounds with an oxathiazolidine-4-one-2,2-dioxide skeleton and their amide synthetic precursors as new anticonvulsant drugs. The cyclic structures were synthesized using a three-step protocol that include solvent-free reactions and microwave-assisted heating. The compounds were tested in vivo through maximal electroshock seizure test in mice. All the structures showed activity at the lower doses tested (30 mg/Kg) and no signs of neurotoxicity were detected. Compound encoded as 1g displayed strong anticonvulsant effects in comparison with known anticonvulsants (ED50 = 29 mg/Kg). First approximations about the mechanisms of action of the cyclic structures were proposed by docking simulations and in vitro assays against sodium channels (patch clamp methods).
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Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos(IIFP)
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Citación
Sabatier, Laureano Leonel; Palestro, Pablo Hernán; Enrique, Andrea Verónica; Pastore, Valentina; Sbaraglini, Maria Laura; et al.; Design, synthesis and biological evaluation of N-substituted α-hydroxyimides and 1,2,3-oxathiazolidine-4-one-2,2-dioxides with anticonvulsant activity; Taylor & Francis Ltd; Journal of Enzyme Inhibition and Medicinal Chemistry; 34; 1; 14-8-2019; 1465-1473
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