Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 20، شماره 4، تیر 2017، صفحه 430-437 اصل مقاله (1.13 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8586 | ||
| نویسندگان | ||
| Asghar Davood* 1؛ Maryam Iman2، 3؛ Hanieh Pouriaiee4؛ Hamed Shafaroodi5؛ Sepideh Akhbari1؛ Leila Azimidoost1؛ Erfan Imani1؛ Somaieh Rahmatpour1 | ||
| 1Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran | ||
| 2Department of Pharmaceutics, Faculty of pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran | ||
| 3Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran | ||
| 4Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran | ||
| 5Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran | ||
| چکیده | ||
| 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. | ||
| کلیدواژهها | ||
| Anticonvulsant؛ Docking؛ MES seizure؛ Phthalimide؛ PTZ seizure؛ Sodium channel | ||
| مراجع | ||
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