Design and synthesis of 4-(4-ethyl-phenyl)-4-oxo-butyric acid (3-oxo-1, 3-diphenyl-propylidene)/[1-(4-chloro-phenyl)-ethylidene]-hydrazide as potential anticonvulsant agents

Some new substituted hydrazone derivatives were designed, synthesized, and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity was established after intrapentoneal administration in one-seizure models, which include maximal electroshock seizure (MES) model. In the MES screen, the most active compounds were PK-1 and PK-2 which showed 100 % protection. None of these compounds showed neurotoxicity. A computational study was also performed including prediction of pharmacokinetic properties, bioactivity, toxicity, and docking studies. The result reveals from the computational studies as the protein-ligand interaction energies of derivatives PK-1 and PK-2 with established epilepsy receptor namely Na/H exchanger were -8.31 and -7.30 kcal/mol, which is slightly higher than the phenytoin as -6.71 kcal/mol. The percentage of absorption (%ABS) was calculated and observed that all titled compounds exhibited a better %ABS ranging 82-90. Therefore, all pharmacological parameters are almost similar to standard drug. The above observation suggested that these compounds would serve as better lead compounds for anticonvulsant screening for future drug design perspective.