Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: A natural product coupled approach to semicarbazones for antiepileptic activity

Two novel series of N4-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N1-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enylidene)semicarbazide and N4-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N1-(3,7-dimethylocta-3,6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. The rotorod test was conducted to evaluate neurotoxicity. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity. The efforts were also made to establish structure–activity relationships among test compounds.

Two novel series of limonene/citral based semicarbazones possessing four vital structural features (A) hydrophobic aryl ring system, (HBD) hydrogen binding domain, (D) electron donor moiety and (C) distal aryl ring required for anticonvulsant activity are disclosed. These compounds have been found to possess anticonvulsant activity through GABA mediation.Figure optionsDownload as PowerPoint slide