K+ Channels and Some Familiar Antiepileptic Drugs: Evaluation of Their the Structure-Activity Relationships with Molecular Docking Analysis

Year 2023, , 305 - 325, 31.05.2023

Esra Nur Çakmak , Mahmut Gür , Bayram Kıran

https://doi.org/10.31202/ecjse.1213826

Abstract

This study includes the structure-activity relationship of active molecules that are commonly used in the treatment of convulsive seizures in epileptic diseases. Well-known epileptic active molecules studied are: Vigabatrin, Lokosamidine, Zonisamide, Oxcarbazepine, Levetiresetam, Tiagabine, Topiramate, Lamotrigin, Gabapentin, Felbamat, Ethosuximide, Valproic Acid, Mesuximide, Ethotoin, Primidon, Trimethadion, Phenytoin, Remasemide, Mephenytoin. These molecules, which were selected considering the physiopathological mechanisms of action of epileptic disease, were considered suitable for molecular docking studies since they were used as a potential antiepileptic agent. In addition, it was focused on the potassium channels, which were prominent in the mechanisms of epilepsy. During the action potential that triggers seizure formation, inward rectifying potassium channels (KIR3.2) make a important role providing the flow of K+ ions.
Thus, PDB ID: 4KFM receptor was chosen for molecular docking study, since its act as an agonist according to its activity on the canal in the case of epileptic seizures formation. The result of molecular docking analysis demonstrated that Phenytoin gave the best binding affinity for 4KFM with a value of -6.2 kcal/mol. Other analysis in descending order (as kcal/mol); Oxcarbazepine (-6,0), Remasemide (-5.9), Topiramate and Primidon (-5.8), Tiagabine, Felbamat and Mesuximide (-5.7), Lamotrigin (-5.6) Zonisamide, Ethotoin and Mephenytoin, Lokosamidine (-5.5), Gabapentin (-4.8), Trimethadion (-4.7), Ethosuximide (-4.6), Levetiresetam (-4.5), Vigabatrin (-4.0), Valproic Acid (-3.9) determined as.

Keywords

Antiepileptic, Drug, Moleculer Docking, Potassium channel, Epilepsy

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