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

IMP metallo-β-lactamases (MBLs) confer broad-spectrum resistance to β-lactam antibiotics such as imipenem and escape the action of almost all clinically used β-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; $$ r_{\text{pre}}^{ 2} = 0. 8 4 3 $$ ) and CoMSIA model (r 2 = 0.968; $$ r_{\text{pre}}^{ 2} = 0. 9 5 7 $$ ). Our work will facilitate the design and optimization of new potential inhibitors.