Synthesis and anticonvulsant activity of new phenytoin derivatives

Hybrids between phenytoin and thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-triazole were synthesized and tested for anticonvulsant activity. Preliminary anticonvulsant screening was performed using standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens in mice. The neurotoxicity was determined applying the rotarod test. Among these compounds, 4 and 5d showed the highest protection (80%) in the scPTZ test at a dose of 100 mg/kg, whereas the compound 5b displayed promising anticonvulsant effect in the MES model.

Graphical abstractHybrid approach was used to design and synthesize hybrids between phenytoin and thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-triazole pharmacophores to examine their anticonvulsant activity using MES and scPTZ screens in mice.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of phenytoin derivatives. ► Anticonvulsant activity of all new synthesized compounds was determined. ► Neurotoxicity of the most active compounds was estimated. ► Compounds 4, 5b and 5d demonstrated marked anticonvulsant effect. ► Elemental analysis and spectroscopic characterization of all new compounds.