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-substi-tuted 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)semicarba-zides 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 thiosemicar-bazone compounds were compared at different doses, 2-(1H-imidazole-1-yl)-1-(2-naphthyl)ethane-1-one N-(3-chloro-phenyl)thiosemicarbazone (3) and 2-(1H-imidazole-1-yl)-1-(2-biphenyl)ethane-1-one N-(4-fluorophenyl)thiosemicarba-zone (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-methylphe-nyl)thiosemicarbazone (14) was the most active compound in the scPTZ-induced seizure test after 4 h. The 2,4-dichloro-phenyl (9) and 2-fluorophenyl (10) substituted biphenyl derivatives of thiosemi-carbazone compounds showed neurotoxicity at higher doses

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

“…Schiff base derivative 196 not only gave remarkable anti‐MES efficacy with an ED 50 value of 30 mg/kg, but also had a suitable lipophilicity for crossing the blood–brain barrier. The meta ‐cholo substitution of benzene ring was vital since activity disappeared with para ‐substitution . The results confirmed the value for further optimization of these compounds as anticonvulsant agents.…”

Crystal structure of 1-(2H-1,3-benzodioxol-5-yl)-3-(1H-imidazol-1-yl)propan-1-one, C13H12N2O3

“…Their current importance is testified by their ubiquitousness in the fields of medicinal chemistry, material science and agrochemicals [1]. Imidazole-based compounds exhibit diverse biological activities anticancer [2][3][4][5] antibacterial [6,7], antitubercular [8,9], antifungal [10,11], antiviral [12][13][14], anticonvulsant [15][16][17] and antiparkinson's agents [18,19]. The [20][21][22].…”

A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment

“…In comparison to its benzimidazole analog, compound 14 revealed an improved BBB penetration efficacy (Wager et al., 2010; Asproni et al., 2011). Compound 15 , a Schiff-base derivative, worked as an effective anti-convulsant candidate agent together with an appropriate liposolubility favoring BBB passage (Caliş et al., 2011). The imidazolium-based compound 16 with a quinoxaline segment was not only a highly 5-HT 3 receptor-targeted drug candidate but also identified to be a good BBB-permeable agent (Butini et al., 2009).…”