Table 1. Inhibitory Concentration of Phosphonamidates (1–2) (IC50) against the Purified Enzymes NDM-1, GIM-1, and VIM-2a.
IC50 (μM) |
|||||||||
---|---|---|---|---|---|---|---|---|---|
enzyme | 1a | 1b | 1c | 1d | 2 | 1e | 1f | 1g | 1h |
NDM-1 | N.I. | 356 | N.I | 430 | N.I. | N.I. | P. | P. | P. |
GIM-1 | 86 | 109 | N.I. | N.I. | N.I. | 2700 | P. | P. | P. |
VIM-2 | N.I. | 1417 | 500 | N.I. | N.I. | N.I. | P. | P. | P. |
IC50 = appKi + (Et/2), where appKi is the apparent Ki, and Et is the enzyme concentration. Accordingly, when the observed IC50 is much greater than the enzyme concentration, it is determined by the apparent Ki and not by the enzyme concentration.21 In the measurements mentioned above, the enzyme concentration has been at least 3 orders of magnitude below the observed IC50 values, and hence, the reported IC50s are in no mean affected by the NDM-1, GIM-1, and VIM-2 concentrations.