Abstract
Eleven analogs of N-arylisoindoline pharmacophore were synthesized and evaluated for their anticonvulsant activities. The in vivo screening data acquired indicate that all the analogs have the ability to protect against pentylenetetrazole-induced seizure. Compounds 2, 6, and 11 elevated clonic seizure thresholds at 30 min which were more active than reference drug phenytoin, and compounds 2, 7, and 11 showed marked anticonvulsant activity on tonic seizure. The most potent compounds were 2 and 11 which had comparative activity to the phenytoin. Using a model of the open pore of the Na channel, we have docked all compounds. Docking studies have revealed that these compounds 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.
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Acknowledgments
We are grateful to the Azad University for financial support of this research, and to Professor Arthur J. Olson and Professor A. Fozzard for their kindness in offering us the AutoDock 4.2 program and model of sodium channel.
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Davood, A., Amini, M., Azimidoost, L. et al. Docking, synthesis, and pharmacological evaluation of isoindoline derivatives as anticonvulsant agents. Med Chem Res 22, 3177–3184 (2013). https://doi.org/10.1007/s00044-012-0256-y
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DOI: https://doi.org/10.1007/s00044-012-0256-y