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

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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.

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Acknowledgements

Financial assistance from the Shiraz University of Medical Sciences by way of Grant Number 95-01-36-13130 and 24020 is gratefully acknowledged.

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Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran

    Leila Emami, Leila Amiri-Zirtol, Masoumeh Divar & Soghra Khabnadideh

  2. Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran

    Leila Moezi & Fatemeh Pirsalami

  3. Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Islamic Republic of Iran

    Aida Solhjoo

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  1. Leila Emami
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Emami, L., Moezi, L., Amiri-Zirtol, L. et al. Anticonvulsant activity, molecular modeling and synthesis of spirooxindole-4H-pyran derivatives using a novel reusable organocatalyst. Mol Divers 26, 3129–3141 (2022). https://doi.org/10.1007/s11030-021-10372-7

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