Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker

Iman, Maryam; Saadabadi, Atefeh; Davood, Asghar

doi:10.22038/ijbms.2013.1684

Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker

Authors

¹ Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

² Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

10.22038/ijbms.2013.1684

Abstract

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.

Keywords

Anticonvulsant Docking Molecular modeling Na channel Phthalimide

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