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Design, Synthesis and Protection Against Pentylenetetrazole-induced Seizure of N-aryl Derivatives of the Phthalimide Pharmacophore

[ Vol. 8 , Issue. 5 ]


Asghar Davood, Hamed Shafaroodi, Mohsen Amini, Alireza Nematollahi, Mehrshad Shirazi and Maryam Iman   Pages 953 - 963 ( 11 )


A series of compounds including N-aryl substituents of phthalimide and 4-nitrophthalimide were synthesized and evaluated for their anticonvulsant properties. The in vivo screening data suggest that all the analogs have the ability to protect against pentylenetetrazole-induced seizures. These compounds exerted their maximal effects 30 min after administration. The most potent compound in both, tonic and clonic seizure was 1-naphthyl derivative (comp. 6), which was more active than the reference drug known as Phenytoin. Using an open pore model of the Na channel, these anticonvulsants were docked in the active site and examined in relation to the residues identified by mutagenesis as important for their binding energies. Docking studies revealed that all compounds (1-13) interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and additional hydrophobic interactions with domain I and II in the channel's inner pore.


Phthalimide, Nitrophthalimide, Seizure, Phenytoin, Epilepsy, Na channel, hydrogen bond, N-phenylphthalimide derivatives, drug, aromatic amines


Department of Medicinal Chemistry, Branch of Pharmaceutical Sciences, Islamic Azad University, Tehran, 19419, Iran, Postal address: No 99, Yakhchal ave. Shariatie Street. Tehran, 19419, Iran.

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