TABLE 2

Time course for the inhibition of metallo-β-lactamases by cyclic boronates 1 and 2 and broad-spectrum thiol-based MBL inhibitorsa

InhibitorPreincubation time (min)IC50, μM (mean ± SD)b for:
BcII, pH 7.5BcII, pH 6.5VIM-1, pH 7.5
102.8 ± 0.23.3 ± 0.11 ± 1
103.0 ± 0.23.8 ± 0.21 ± 1.2
302.8 ± 0.33.5 ± 0.11 ± 1.5
603.4 ± 0.33.8 ± 0.21.4 ± 0.3
3603.1 ± 0.23.0 ± 0.21.2 ± 0.3
200.45 ± 0.020.27 ± 0.020.061 ± 0.001
100.45 ± 0.020.20 ± 0.010.085 ± 0.002
300.36 ± 0.020.20 ± 0.010.088 ± 0.001
600.36 ± 0.010.20 ± 0.010.083 ± 0.002
3600.36 ± 0.030.23 ± 0.010.061 ± 0.001
l-Captopril013.7 ± 0.317.4 ± 0.31.91 ± 0.06
1021 ± 120.4 ± 0.62.3 ± 0.2
3012.5 ± 0.516.8 ± 0.82.4 ± 0.2
6014.6 ± 0.413.7 ± 0.72.6 ± 0.1
36015 ± 116.3 ± 0.52.8 ± 0.2
(±)-Thiomandelic acid00.30 ± 0.030.27 ± 0.060.38 ± 0.03
100.39 ± 0.050.9 ± 0.10.45 ± 0.02
300.33 ± 0.040.5 ± 0.10.8 ± 0.9
600.5 ± 0.22 ± 11.4 ± 0.9
3602 ± 12 ± 12 ± 1
  • a FC5 was used as a substrate (22).

  • b IC50s were taken after preincubation of the enzyme with the corresponding inhibitor for 0, 10, 30, 60, or 360 min prior to assay. IC50s were obtained from fitting of residual activity plots using GraphPad Prism.