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

Publish Year: 1396
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:

JR_IJBMS-20-4_012

تاریخ نمایه سازی: 28 مهر 1400

Abstract:

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 ۲-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 ۳ and ۹ elevated clonic seizure thresholds at ۳۰ min which were more active than the standard medicine phenytoin. Compounds ۳, ۶, ۷, ۱۱, ۱۳ and ۱۴ with ۱۰۰% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound ۳. 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-S۶ of NaV۱.۲ 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.

Authors

Asghar Davood

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

Maryam Iman

Department of Pharmaceutics, Faculty of pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

Hanieh Pouriaiee

Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran

Hamed Shafaroodi

Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Sepideh Akhbari

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

Leila Azimidoost

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

Erfan Imani

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

Somaieh Rahmatpour

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

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