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

摘要

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.