Fig. 2: Evaluation of VIM-2, GIM-1 and NDM-1 inhibitory activities of 5a–m.
From: Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors
a Inhibitory activities (IC50) against the purified metallo-β-lactamases VIM-2, GIM-1 and NDM-1, and cytotoxicities (CC50) against HepG2 cells. Activities in the low μM range were observed for each of the three enzymes (in magenta), and several inhibitors showed activity against more than one of them. Some of the compounds showed absorbance interference with the substrate, which prevented the evaluation of their activity (no value given). Estimated inhibition constants (Ki) for VIM-2, GIM-1, and NDM-1 are given in Supplementary Table S3. b Normalized relative activity of metallo-β-lactamases encapsulated in outer membrane vesicles in absence (buffer) and presence of inhibitors. Error bars represent the standard deviation of four measurements. All compounds were used at a final concentration of 100 µM. c, d Effect of the inhibitors on ampicillin-clavulanic acid (AMC) growth inhibition zone diameters. AMC zone inhibition diameters were measured for E. coli TOP10 (wt, magenta column, c), E. coli TOP10xpCR4-Vim-2 (VIM-2, green column, c). Inhibitors 5a–l were added to AMC containing discs and inhibition zone diameters were recorded for E. coli TOP10 × pCR4-VIM-2 (blue columns, c). Columns represent the mean of two independent experiments. Several compounds show inhibition of VIM-2 activity (green squares) as compared to the control samples (blue circles, d). Error bars represent the standard deviation.
