TABLE 1

Time course for the inhibition of serine-β-lactamases (classes A, C, and D) by cyclic boronates 1 and 2 and established inhibitors that act by formation of a stable acyl-enzyme complexa

InhibitorPreincubation time (min)IC50, nM (mean ± SD)b for:
TEM-1CTX-M-15AmpCOXA-23OXA-48
Cyclic boronate 102.6 ± 0.192 ± 668 ± 3220 ± 1140 ± 1
101.3 ± 0.113 ± 19.8 ± 0.3250 ± 1160 ± 1
301.6 ± 0.13.7 ± 0.14.5 ± 0.1260 ± 1170 ± 1
601.5 ± 0.11.7 ± 0.12.6 ± 0.1270 ± 1170 ± 1
3601.7 ± 0.14.0 ± 0.012.4 ± 0.1730 ± 2270 ± 1
Cyclic boronate 208.1 ± 0.139 ± 2270 ± 602,000 ± 1002,000 ± 100
103.4 ± 0.17.5 ± 0.3120 ± 102,600 ± 1002,600 ± 200
302.6 ± 0.12.8 ± 0.1150 ± 103,300 ± 2003,400 ± 100
602.6 ± 0.11.3 ± 0.1100 ± 102,600 ± 1003,000 ± 100
3602.1 ± 0.16.4 ± 0.196 ± 13,300 ± 2003,300 ± 200
Sulbactam0860 ± 8044 ± 1>2 × 105>2 × 105>2 × 105
10600 ± 20029 ± 142,000 ± 2,000>2 × 105>2 × 105
30600 ± 20028 ± 78,600 ± 600>2 × 105>2 × 105
60500 ± 20032.0 ± 0.34,400 ± 500>2 × 105>2 × 105
360700 ± 30016.6 ± 0.11,000 ± 400>2 × 105>2 × 105
Avibactam019 ± 19.9 ± 0.21,400 ± 400770 ± 42500 ± 30
103.4 ± 0.11.1 ± 0.1190 ± 10390 ± 1810 ± 50
302.2 ± 0.10.40 ± 0.06200 ± 10160 ± 2300 ± 2
602.0 ± 0.10.39 ± 0.01200 ± 1071 ± 1150 ± 1
3604.3 ± 0.16.4 ± 0.1150 ± 1013 ± 120 ± 1
BLI-48904.8 ± 0.232 ± 2210 ± 205.6 ± 0.114 ± 1
102.0 ± 0.16.9 ± 0.230 ± 15.6 ± 0.115 ± 1
301.7 ± 0.22.2 ± 0.112.0 ± 0.46.2 ± 0.116 ± 1
601.7 ± 0.10.94 ± 0.035.6 ± 0.18.6 ± 0.122 ± 1
3601.9 ± 0.18.0 ± 0.11.9 ± 0.118 ± 149 ± 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.