Anticonvulsant activity, molecular modeling and synthesis of spirooxindole-4H-pyran derivatives using a novel reusable organocatalyst

Abstract

Fifteen derivatives of spirooxindole-4H-pyran (A₁-A₁₅) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ)-induced epilepsy mouse models. Four doses of the compounds (20, 40, 60 and 80 mg/kg) were tested in comparison with diazepam as positive control. The resulted revealed that compounds A₃ and A₁₂ were the most active compounds and indicated significant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no significant decrease in its catalytic action. In silico assessment of physicochemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding affinities as γ-aminobutyric acid-A (GABA-A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.

Keywords: 1-(2-Aminoethyl) piperazine; Anticonvulsant; Graphene oxide; Mice; Molecular docking; Pentylenetetrazole; Spirooxindole-4H-pyran.