TY - JOUR ID - 8586 TI - Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Davood, Asghar AU - Iman, Maryam AU - Pouriaiee, Hanieh AU - Shafaroodi, Hamed AU - Akhbari, Sepideh AU - Azimidoost, Leila AU - Imani, Erfan AU - Rahmatpour, Somaieh AD - Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran AD - Department of Pharmaceutics, Faculty of pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran AD - Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran AD - Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Y1 - 2017 PY - 2017 VL - 20 IS - 4 SP - 430 EP - 437 KW - Anticonvulsant KW - Docking KW - MES seizure KW - Phthalimide KW - PTZ seizure KW - Sodium channel DO - 10.22038/ijbms.2017.8586 N2 - 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. UR - https://ijbms.mums.ac.ir/article_8586.html L1 - https://ijbms.mums.ac.ir/article_8586_09ccb430c0f02e1c24ea319f9072bb44.pdf ER -