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

Abstract

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

Synthesis and Evaluation of Aminothiazole Hybrids as Potential Acetylcholinesterase Inhibitors

“…The oxadiazole moiety is considered to have varied medicinal actions like anti-alzheimer [30,32], anti-inflammatory [33], antimicrobial [34], antimalarial [35], antidepressant [36], analgesic [37], anticancer [38] and antiviral [39], etc. Also, the multifunctional nature of the 1,3,4-oxadiazole nucleus with different substitutions has been reported for significant anticholinesterase and antioxidant activities [32,40].…”

Unveiling the chemistry of 1,3,4‐oxadiazoles and thiadiazols: A comprehensive review

“…SAR study of these derivatives indicated that only those compounds with electron‐donating capacity showed moderate activity, while the electron‐withdrawing groups showed weak activity in the protein denaturation assay. [ 39 ]…”

“…SAR study of these derivatives indicated that only those compounds with electron-donating capacity showed moderate activity, while the electron-withdrawing groups showed weak activity in the protein denaturation assay. [39] Basappa et al synthesized a number of substituted 3-(5-phenyl-1,3,4-oxadiazol-2-yl)−2H-chromene-2-ones using a grinding approach with substituted aldehydes and analogs of hydrazine hydrates in the presence of iodine, which facilitates the process of cyclization. The synthesized chemical structures were assessed using spectroscopic techniques such as IR, 1 H NMR, 13 C NMR, and LCMS.…”