Synthesis, Anticonvulsant
Activity and In silco Studies of Schiff Bases of
2-Aminothiophenes via Guanidine-Catalyzed Gewald
Reaction
Pavan Kumar Kunda1*,
J Venkateswara Rao2, K Mukkanti3,
Madhusudhanareddy Induri4 and G Deepak 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:
Email:
pavanreddy79@gmail.com Tel:
+91-9160044376
Received: 6 July 2012
Revised accepted: 17 June
2013
Tropical Journal of
Pharmaceutical Research, August 2013; 12(4): 566-576
http://dx.doi.org/10.4314/tjpr.v12i4.19
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
