Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine-Catalyzed Gewald Reaction

Pavan Kumar Kunda¹ , Venkateswara J Rao², K Mukkanti³, Madhusudhanareddy Induri⁴, Deepak G Reddy⁵

¹Department of Pharmaceutical Chemistry, CM College of Pharmacy, Maisammaguda, Dhulapally, Secunderabad; ²Department of Pharmaceutical Chemistry & Pharmaceutical Analysis, Sultan-ul-uloom College of Pharmacy, Banjara Hills; ³Director IST, JNTUH, Hyderabad; ⁴Department of Pharmaceutical Chemistry, Malla Reddy College of Pharmacy, Maisammaguda, Secunderabad; ⁵Research Division, Dept. of Medicinal Chemistry, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Andhra Pradesh, India.

For correspondence:- Pavan Kunda Email: pavanreddy79@gmail.com Tel:+919160044376

Received: 6 July 2012 Accepted: 17 June 2013 Published: 23 August 2013

Citation: Kunda PK, Rao VJ, Mukkanti K, Induri M, Reddy DG. Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine-Catalyzed Gewald Reaction. Trop J Pharm Res 2013; 12(4):566-576 doi: 10.4314/tjpr.v12i4.19

© 2013 The authors.
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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 electroshock-induced seizure (MES), and pentylenetetrazole-induced seizure (PTZ) against phenytoin and diazepam as reference standards. Molecular docking (in silico) studies were performed using 4-aminobutyrate-aminotransferase 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