title: A new class of anticonvulsants possessing 6 Hz psychomotor seizure test activity: 2-(1H-benzotriazol-1-yl)-N'-[substituted] acetohydrazides.
abstract: A series of 2-(1H-Benzotriazol-1-yl)-N'-[substituted]acetohydrazides were designed & synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The new compounds were characterized using FT-IR, 1H NMR, mass spectral data and elemental analysis. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The neurotoxicity was assessed using the rotorod method. The most active compound of the series was N'-[4-(1,3-Benzodioxol-5-yloxy)benzylidene]-2-(1H-benzotriazol-1-yl)acetohydrazide (BTA 9), which showed good activity with 75 % protection (3/4, 0.5 h) at a dose of 100 mg/kg in mice. All the compounds exhibited no neurotoxicity. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta, GABA (A) alpha-1 receptors and Na/H exchanger, in Lamarckian genetic algorithm based flexible docking studies.
authors.affiliation: S. D. College of Pharmacy and Vocational Studies, Bhopa Road, Muzaffarnagar, 251001, U.P., India. praveensha1977@rediffmail.com
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Laxmi
authors.initials: L
authors.lastname: Tripathi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D019295:Computational Biology; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy*; D012984:Software
chemical_list: D000927:Anticonvulsants; D006834:Hydrazines