Abstract

Antiepileptic drugs are used to prevent or reduce the occurrence of epileptic seizures, but up to 30 of patients are resistant to the available medical therapies. Ten new analogs of 2-aryl substituent of isoindoline-1,3-dione have been synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect mice against pentylenetetrazole-induced seizures. These compounds exerted their maximal effects 30 min after administration. The most potent compound was 4-triazolyl derivative (compound VIII). Using a model of the open pore of the Na channel, we have docked compound VIII. Docking studies have revealed that this ligand (i) interacts mainly with residues II-S6 of NaV1.2 by forming hydrogen bonds and (ii) has additional hydrophobic interactions with domains I and II in the channel inner pore.