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

SABATIER LAUREANO; PALESTRO PABLO; ENRIQUE ANDREA; PASTORE VALENTINA; SBARAGLINI MARIA LAURA; MARTIN PEDRO; GAVERNET LUCIANA

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2019

1475-6366

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 cy-clic 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).