Three-dimensional quantitative structure-activity relationship (CoMSIA) analysis of bis-coumerine analogues as urease inhibitors

As a basis for predicting structural features that may lead to the design of more potent and selective inhibitors of urease, the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of 30 bis-coumerine analogs, which are known urease inhibitors. Five different properties: steric, electrostatic, hydrophobic, H-bond donor, and H-bond acceptor, assumed to cover the major contributions to ligand binding, were used to generate the 3D-QSAR model. A significant cross-validated correlation coefficient q(2) (0.51), r(2) (0.962) for CoMSIA were obtained, indicating the statistical significance of this class of compounds. Actual urease inhibitory activities of this class, and the predicted values were in good agreement with the experimental results. This model offer insight into the structural requirements for activity of bis-coumerine analogues as urease inhibitors, since there is only speculative knowledge of their target in protein.