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 L.; PALESTRO, PABLO H.; ENRIQUE, ANDREA V.; PASTORE, VALENTINA; SBARAGLINI, MARÍA L.; MARTÍN, PEDRO; GAVERNET, LUCIANA

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

TAYLOR & FRANCIS LTD

Año: 2019 vol. 34 p. 1465 - 1473

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 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).