Various derivatives of imidazole-2-thione are reported to possess antimicrobial activity. A Quantitative Structure Activity Relationship (QSAR) study was carried out on 1-tolyl-3-aryl-4-methylimidazole-2-thiones to examine the structural requirement for antimicrobial activity against E coli. The QSAR study was performed using CS Chem. Office 2005 and vLife MDS 3.5 molecular modeling software. Energy minimization of all the derivatives were carried out using CS Chem. Office 2001 by Allingers MM2 force field where the Root Mean Square Gradient (RMS) at 0.1 kcal mol-1 and semiemperical AM1 Hamiltonian method (MOPAC module). The thermodynamic, steric and electronic descriptors were calculated using vLife MDS 3.5 molecular modeling software. Antibacterial activity data and various molecular descriptors were taken as dependent and independent variables respectively and correlation was established between them by employing stepwise multiple linear regression method. In order to explore the predictive power of the selected descriptors, the data set of 25 imidazole-2-thione derivatives was divided into training set (18 compounds) and test set (7 compounds). Several stepwise multiple linear regressions were performed using vLifeMDS 3.5, in order to obtain QSAR models. Among the many correlations generated, statistically significant models were selected based on various statistical measures employed for the evaluation of the significance of the model. The orthogonality of the descriptors in the selected correlations was confirmed by the calculation of overall correlation matrix. The results of the study emphasize the importance of electronic parameter on antibacterial activity of imidazolidine-2-thiones against E coli. Polarizability and dipole moment of the molecules have major effects on the antibacterial activity of 1-tolyl-3-aryl-4-methylimidazole-2-thiones.
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