Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction
Abstract
Purpose: To synthesize Schiff bases of 2-aminothiophenes and evaluate their anticonvulsant activity and in silco properties
Methods: 2-Amino-N-o-tolyl-5,6-dihydro-4H-cylcopenta[b]thiophene-3-carboxamide was synthesized using 1,1,3,3-tetramethylguanidine lactate as a basic catalyst and by microwave irradiation. 2- substitued-o-tolyl-5,6-dihyro-4H-cylcopenta[b]thiophene-3-carboxamide was prepared by reacting with different substituted aromatic aldehydes. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against maximum electroshockinduced seizure (MES), and pentylenetetrazole-induced seizure (PTZ) against phenytoin and diazepam as reference standards. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions.
Results: Among the 21 synthesized compounds, 2b, 2d, 2f, 2k, 2m, 2n and 2o showed good to moderate activity against MES and PTZ-induced convulsions. Compounds 2b, 2d, 2f, 2k and 2m exhibited lower activity against PTZ than against MES model while compounds 2n and 2o afforded greater protection against PTZ than against MES model. In silico results also revealed maximum binding affinity to GABA-AT protein which was higher than other compounds
Conclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.
Keywords: Ionic liquid, 2-Aminothiophenes, Anticonvulsant, In silco studies, Molecular docking.
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