Introduction: In this study, fifteen new 2,5-disubstituted analgouges of phthalimide were
designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity
against the Maximal Electroshock (MES) and subcutaneous Pentylenetetrazole (scPTZ) compare to
phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FTIR,
H-NMR, C-NMR and MASS spectroscopy.
Methods: All the tested compounds were found to be effective in the PTZ model at dose of 60 mg/kg
and most of the compounds showed protection against MES test indicative of their ability to inhibit the
seizure spread at all dose ranges. Compound 3 illustrated the best efficacy among all compounds and
showed more potency than phenytoin in clonic seizure and was potent as phenytoin in tonic seizure.
Results & Discussion: Using a model of the Na channel, these derivatives were docked in the active
site. Docking studies displayed that all synthesized compounds have more negative binding energy
compare to reference drug and inhibition-constant less than phenytoin that means they can block the
receptor more efficiently and usually form hydrophobic interactions or hydrogen bond interaction frequently
with the domains I, II, III and rarely with domain IV.