title: Synthesis and anticonvulsant evaluation of some novel (thio)semicarbazone derivatives of arylalkylimidazole.
abstract: A number of novel 2-(1H-imidazole-1-yl)-1-aryl-substituted ethane-1-one N-substituted phenyl(thio)semicarbazones (1-14) were synthesized to test for their anticonvulsant activity against the two seizure models, maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ). Title compounds were prepared by the reaction of appropriate (thio)semicarbazides with ketones. Neurotoxicity was screened by the rotarod test. The structure of compounds was confirmed by elemental analysis results and the spectroscopic techniques such as IR, 1H-NMR, 13C-NMR, ESI-MS and HRMS. As a result of activity studies, when the thiosemicarbazone compounds were compared at different doses, 2-(1H-imidazole-1-yl)-1-(2-naphthyl)ethane-1-one N-(3-chlorophenyl)thiosemicarbazone (3) and 2-(1H-imidazole-1-yl)-1-(2-biphenyl)ethane-1-one N-(4-fluorophenyl) thiosemicarbazone (12) were found selective and highly active compounds against MES-induced seizures after 0.5 h and 4 h, respectively. Beside this, 2-(1H-imidazole-1-yl)-1-(1-biphenyl)ethane-1-one N-(4-methylphenyl)thiosemicarbazone (14) was the most active compound in the scPTZ-induced seizure test after 4 h. The 2,4-dichlorophenyl (9) and 2-fluorophenyl (10) substituted biphenyl derivatives of thiosemicarbazone compounds showed neurotoxicity at higher doses.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey. ucalis@hacettepe.edu.tr
authors.forename: Unsal
authors.initials: U
authors.lastname: Caliş
authors.forename: Ebubekir
authors.initials: E
authors.lastname: Septioğlu
authors.forename: Mutlu Dilsiz
authors.initials: MD
authors.lastname: Aytemir
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D003292:Convulsants; D004597:Electroshock; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D012664:Semicarbazones / Q000138:chemical synthesis; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D007093:Imidazoles; D007202:Indicators and Reagents; D012664:Semicarbazones; D013882:Thiosemicarbazones; D010433:Pentylenetetrazole