OBJECTIVEA series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity.

METHODSAll the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test.

RESULTSA majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens.

CONCLUSIONThe results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

Animals ; Anticonvulsants ; administration & dosage ; adverse effects ; analysis ; chemistry ; Drug Evaluation, Preclinical ; Injections, Intraperitoneal ; Levulinic Acids ; administration & dosage ; adverse effects ; analysis ; chemistry ; Mice ; Seizures ; drug therapy ; Semicarbazones ; administration & dosage ; adverse effects ; analysis ; chemistry ; Treatment Outcome