Design, synthesis and biological evaluation of N-substituted α-hydroxyimides and 1,2,3-oxathiazolidine-4-one-2,2-dioxides with anticonvulsant activity

• Autores: Sabatier, Laureano Leonel; Palestro, Pablo Hernán; Enrique, Andrea Verónica; Pastore, Valentina; Sbaraglini, María Laura; Martín, Pedro; Gavernet, Luciana
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ciencias Exactas; Epilepsy; 1,2,3- oxathiazolidine-4-one-2,2- dioxide; α-hydroxyimides; docking; sodium channels blockers; MES test; microwaveassisted synthesis
• Institución: Universidad Nacional de La Plata

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).
Facultad de Ciencias Exactas
Instituto de Estudios Inmunológicos y Fisiopatológicos