title: Design, synthesis and evaluation of benzofuran-acetamide scaffold as potential anticonvulsant agent.
abstract: A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran- 3-yl)-2-(substituted)-acetamide derivatives (4a-l, 5a-l) was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES) model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1) body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine) strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Shakya
authors.forename: Mehnaz
authors.initials: M
authors.lastname: Kamal
authors.forename: Vishal M
authors.initials: VM
authors.lastname: Balaramnavar
authors.forename: Sanna K
authors.initials: SK
authors.lastname: Bardaweel
authors.forename: Rajashri R
authors.initials: RR
authors.lastname: Naik
authors.forename: Anil K
authors.initials: AK
authors.lastname: Saxena
authors.forename: H H
authors.initials: HH
authors.lastname: Siddiqui
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000737:chemistry / Q000378:metabolism*; D000081:Acetamides / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D001572:Benzofurans / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D001665:Binding Sites; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018755:GABA Agonists / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D007928:Lethal Dose 50; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism; D017208:Rats, Wistar; D012640:Seizures / Q000517:prevention & control*; D034421:Sus scrofa; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D001572:Benzofurans; D018755:GABA Agonists; C000613658:N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1-yl)acetamide; C000613657:N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl(methyl)amino)acetamide; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005998:Glycine