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Iranian Journal of Basic Medical Sciences، جلد ۲۰، شماره ۴، صفحات ۴۳۰-۴۳۷
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عنوان انگلیسی Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models
چکیده انگلیسی مقاله 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.
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نویسندگان مقاله اصغر داود | asghar davood
department of medicinal chemistry, faculty of pharmacy, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

مریم ایمان | maryam iman
department of pharmaceutics, faculty of pharmacy, baqiyatallah university of medical sciences, tehran, iran|chemical injuries research center, baqiyatallah university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی بقیه الله (Baqiyatallah university of medical sciences)

هانیه pouriaiee | hanieh pouriaiee
department of pharmacology and toxicology, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

حامد شفارودی | hamed shafaroodi
department of pharmacology, faculty of medicine, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

سپیده اخباری | sepideh akhbari
department of medicinal chemistry, faculty of pharmacy, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

لیلا azimidoost | leila azimidoost
department of medicinal chemistry, faculty of pharmacy, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

عرفان ایمانی | erfan imani
department of medicinal chemistry, faculty of pharmacy, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

سمیه رحمت پور | somaieh rahmatpour
department of medicinal chemistry, faculty of pharmacy, pharmaceutical sciences branch, islamic azad university, tehran, iran

سازمان اصلی تایید شده: دانشگاه آزاد اسلامی علوم و تحقیقات (Islamic azad university science and research branch)

نشانی اینترنتی http://ijbms.mums.ac.ir/article_8586.html
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