title: Aptiom (eslicarbazepine acetate) as a dual inhibitor of β-secretase and voltage-gated sodium channel: advancement in Alzheimer's disease-epilepsy linkage via an enzoinformatics study.
abstract: Neurodegenerative disorders are increasingly identified as one of the major causes of epilepsy. The relationship of epileptic activity to Alzheimer's disease (AD) is of clinical importance. Voltage-gated sodium channel (VSC) is one of the best targets in the treatment of epilepsy while β-secretase (BACE) has long been observed as a curative target for AD. To explore a possible link between the treatment of AD and epilepsy, the molecular interactions of recently Food and Drug Administration approved antiepileptic drug Aptiom (Eslicarbazepine acetate) with BACE and VSC were studied. Docking study was performed using 'Autodock4.2'. Hydrophobic and pi-pi interactions play critical role in the correct positioning of Eslicarbazepine acetate within the catalytic site of VSC and BACE enzyme to permit docking. Free energy of binding (ΔG) of 'Eslicarbazepine acetate-VSC' interaction and 'Eslicarbazepine acetate-CAS domain of BACE' interaction was found to be -5.97 and -7.19 kcal/mol, respectively. Hence, Eslicarbazepine acetate might act as a potent dual inhibitor of BACE and VSC. However, scope still remains in the determination of the three-dimensional structure of BACE-Eslicarbazepine acetate and VSC-Eslicarbazepine acetate complexes by X-ray crystallography to validate the described data. Further, Aptiom (Eslicarbazepine acetate) could be expected to form the basis of future dual therapy against epilepsy associated neurological disorders.
authors.forename: Sibhghatulla
authors.initials: S
authors.lastname: Shaikh
authors.forename: Syed M D
authors.initials: SM
authors.lastname: Rizvi
authors.forename: Nida
authors.initials: N
authors.lastname: Hameed
authors.forename: Deboshree
authors.initials: D
authors.lastname: Biswas
authors.forename: Mahiuddin
authors.initials: M
authors.lastname: Khan
authors.forename: Shazi
authors.initials: S
authors.lastname: Shakil
authors.affiliation: Department of Bio-Engineering, Integral University, Lucknow 226026, India. shazibiotech@gmail.com.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000494:pharmacology*; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology*; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism
chemical_list: D003984:Dibenzazepines; D011480:Protease Inhibitors; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; C416835:eslicarbazepine acetate; D053829:Amyloid Precursor Protein Secretases