Abstract
A three-dimensional quantitative structure – activity relationship (3D-QSAR) study was performed on a series of 1, 3, 4-thiadiazole derivatives reported as anticonvulsant employing self-organizing molecular field analysis (SOMFA) techniques to investigate the structural requirements for the design of novel anticonvulsant. The training set composed of twenty two 1, 3, 4-thiadiazole derivatives that exhibit a potent activity in MMS test while predictive power was evaluated using a test set of 7 molecules. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of 1, 3, 4-thiadiazole in order to interpret graphically the SOMFA results in terms of master grids showing various field contributions. The present 3D-QSAR studies yielded stable and statistically robust models indicated by the moderate cross correlation coefficients which may prove to be a guideline for design of novel anticonvulsants.
Keywords: Anticonvulsant, epilepsy, thiadiazole, 3D-QSAR, CoMFA, SOMFA, 3D QSAR Studies, 1, 3, 4-Thiadiazole Derivatives, structure, –, activity relationship, MMS test, central nervous system, Maximal Metrazol Seizures, aryl semicarbazones, Phenobarbitone, Rufinamide, Phenytoin, Lamotrigine, Carbamazepine, carbonic anhydrase inhibitory activity, Molecular Modeling, Hamiltonian approximations Austin model, MOPAC module, root mean square (RMS) gradient, SOMFA 3D-QSAR Models, PLS analysis, 1Å grid, SOMFA analysis, 3D-QSAR models, Histogram of SOMFA residual value, SOMFA derived Electrostatic grids
Medicinal Chemistry
Title: 3D QSAR Studies on 1, 3, 4-Thiadiazole Derivatives: An Approach to Design Novel Anticonvulsants
Volume: 6 Issue: 4
Author(s): Suresh Thareja, Saurabh Aggarwal, Abhilasha Verma, Tilak Raj Bhardwaj and Manoj Kumar
Affiliation:
Keywords: Anticonvulsant, epilepsy, thiadiazole, 3D-QSAR, CoMFA, SOMFA, 3D QSAR Studies, 1, 3, 4-Thiadiazole Derivatives, structure, –, activity relationship, MMS test, central nervous system, Maximal Metrazol Seizures, aryl semicarbazones, Phenobarbitone, Rufinamide, Phenytoin, Lamotrigine, Carbamazepine, carbonic anhydrase inhibitory activity, Molecular Modeling, Hamiltonian approximations Austin model, MOPAC module, root mean square (RMS) gradient, SOMFA 3D-QSAR Models, PLS analysis, 1Å grid, SOMFA analysis, 3D-QSAR models, Histogram of SOMFA residual value, SOMFA derived Electrostatic grids
Abstract: A three-dimensional quantitative structure – activity relationship (3D-QSAR) study was performed on a series of 1, 3, 4-thiadiazole derivatives reported as anticonvulsant employing self-organizing molecular field analysis (SOMFA) techniques to investigate the structural requirements for the design of novel anticonvulsant. The training set composed of twenty two 1, 3, 4-thiadiazole derivatives that exhibit a potent activity in MMS test while predictive power was evaluated using a test set of 7 molecules. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of 1, 3, 4-thiadiazole in order to interpret graphically the SOMFA results in terms of master grids showing various field contributions. The present 3D-QSAR studies yielded stable and statistically robust models indicated by the moderate cross correlation coefficients which may prove to be a guideline for design of novel anticonvulsants.
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Thareja Suresh, Aggarwal Saurabh, Verma Abhilasha, Raj Bhardwaj Tilak and Kumar Manoj, 3D QSAR Studies on 1, 3, 4-Thiadiazole Derivatives: An Approach to Design Novel Anticonvulsants, Medicinal Chemistry 2010; 6 (4) . https://dx.doi.org/10.2174/1573406411006040233
DOI https://dx.doi.org/10.2174/1573406411006040233 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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