docking studies of phthalimide pharmacophore as a sodium channel blocker

objective(s): recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. the ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (no2, nh2 , me, cl, cooh, meo) at 2-, 3-, and 4- position of the n-phenyl ring and n-(3-amino-2-methylphenyl) succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels.   materials and methods : chemical structures of all compounds were designed using hyperchem program and conformational studies were performed through semi-empirical molecular orbital calculations method followed by pm3 force field. total energy gradient calculated as a root mean square (rms) value, until the rms gradient was 0.01 kcal mol-1. among all energy minima conformers, the global minimum of compounds was used in docking calculations. using a model of the open pore of na channels, docking study was performed by autodock4.2 program. results : docking studies have revealed that these types of ligands interacted mainly with ii-s6 residues of nav1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain i, ii, iii and iv in the channel's inner pore. conclusion   : these computational studies have displayed that these compounds are capable of inhibiting na channel, efficiently.