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

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DAVOOD ASGHAR; IMAN MARYAM; Pouriaiee Hanieh; SHAFAROODI HAMED; Akhbari Sepideh; Azimidoost Leila; Imani Erfan; Rahmatpour Somaieh

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Journal: Iranian Journal of Basic Medical Sciences Year:2017 | Volume:20 | Issue:4 Page(s): 430-437

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Title

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

Author(s)

Keywords

Anticonvulsant

Docking

MES seizure

Phthalimide

PTZ seizure

Sodium channel

Abstract

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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APA: Copy

DAVOOD, ASGHAR, IMAN, MARYAM, Pouriaiee, Hanieh, SHAFAROODI, HAMED, Akhbari, Sepideh, Azimidoost, Leila, Imani, Erfan, & 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), 430-437. SID. https://sid.ir/paper/723766/en

Vancouver: Copy

DAVOOD ASGHAR, IMAN MARYAM, Pouriaiee Hanieh, SHAFAROODI HAMED, Akhbari Sepideh, Azimidoost Leila, Imani Erfan, Rahmatpour Somaieh. Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2017;20(4):430-437. Available from: https://sid.ir/paper/723766/en

IEEE: Copy

ASGHAR DAVOOD, MARYAM IMAN, Hanieh Pouriaiee, HAMED SHAFAROODI, Sepideh Akhbari, Leila Azimidoost, Erfan Imani, and Somaieh Rahmatpour, “Novel derivatives of phthalimide with potent anticonvulsant activity in PTZ and MES seizure models,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 20, no. 4, pp. 430–437, 2017, [Online]. Available: https://sid.ir/paper/723766/en

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