Docking-based 3D-QSAR modeling of the inhibitors of IMP metallo-β-lactamase

IMP metallo-beta-lactamases (MBLs) confer broad-spectrum resistance to beta-lactam antibiotics such as imipenem and escape the action of almost all clinically used beta-lactamase inhibitors. We conducted three-dimensional quantitative structure-activity relationships (3D-QSAR) for a series of IMP-1 MBL inhibitors with the aid of docking-based alignment. While the 3D-QSAR models were created based on a training set of 41 compounds, their external predictivity was validated using a test set of eight compounds. The study has resulted in two types of satisfactory 3D-QSAR models for predicting the biological activity of new compounds: CoMFA model (r (2) = 0.989; ) and CoMSIA model (r (2) = 0.968; ). Our work will facilitate the design and optimization of new potential inhibitors.