Synthesis and anticonvulsant evaluation of some novel (thio)semicarbazone derivatives of arylalkylimidazole

Çalış U., SEPTIOGLU E., Aytemir M. D.

ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH, vol.61, no.6, pp.327-334, 2011 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 61 Issue: 6
  • Publication Date: 2011
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.327-334
  • Hacettepe University Affiliated: Yes


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, (1)H-NMR, (13)C-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.