Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models

Davood, Asghar and Iman, Maryam and Pouriaiee, Hanieh and Shafaroodi, Hamed and Akhbari, Sepideh and Azimidoost, Leila and Imani, Erfan and Rahmatpour, Somaieh (2017) Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models. Iranian Journal of Basic Medical Sciences, 20 (4). pp. 430-437.

IJBMS_Volume 20_Issue 4_Pages 430-437.pdf

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Objective(s): Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents. Materials and Methods: Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models. Results: The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100 protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore. Conclusion: Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures.

Item Type: Article
Subjects: QU Biochemistry
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 22 Sep 2017 22:18
Last Modified: 22 Sep 2017 22:18

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