Synthesis, in silico Studies, and Anticonvulsant Activity of 1,3,4-Oxadiazole Derivatives

The title compounds 1,3,4-oxadiazole derivatives (C1-5) were synthesized by the cyclization of 4-hydroxy benzhydrazide (1) with various substituted aromatic aldehydes (2) in the presence of ceric ammonium nitrate. The structures of the newly synthesized compounds were established based on FT-IR, 1H-NMR, and Mass spectral data. In silico analysis was carried out using the Schrodinger 2018-3 suite device Maestro and docked to the binding site of the Human GABAA receptor (PDB ID:4COF). The toxicity of the compounds was predicted using the LAZAR (Lazy structure-activity relationship) program. The invivo anticonvulsant study was performed by means of a maximal electroshock test and pentylenetetrazole (PTZ)-induced seizures. Compounds C4&C5 showed the highest docking score of −5.676 and −5.277, respectively, and compounds C4&C5 showed the most increased in vivo anticonvulsant activity when compared with the reference drugs in both the PTZ and MES test methods. HIGHLIGHTS A new series of 1,3,4-oxadiazoles (C1-C5) were synthesized by reacting aromatic aldehydes and 4-hydroxy benzhydrazide using cerric ammonium nitrate as (CAT) catalyst and characterized by spectral data All the new compounds were subjected for In-silico analysis and docked to Human GABAA receptor (PDB ID:4COF) In-vivo anticonvulsant activity was carried out for all the new compounds by using maximal electroshock (MES) and pentylenetetrazole (PTZ) models Some of the tested compounds C4&C5 displayed promising anticonvulsant activity GRAPHICAL ABSTRACT