3D QSAR Studies on 1, 3, 4-Thiadiazole Derivatives: An Approach to Design Novel Anticonvulsants

Suresh      Thareja; Saurabh      Aggarwal; Abhilasha      Verma; Tilak      Raj Bhardwaj; Manoj      Kumar

doi:10.2174/1573406411006040233

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