Table 3. Enzyme Inhibition, Potentiation, and Solubility of Side-Chain Phenyl and Pyridyl Analogues.
| compound | X | Y | Z | NDM-1 IC50 μM (MEM MIC, μg/mL)a | VIM-1 IC50 μM | IMP-1 IC50 μM | VIM-2 IC50 μM | solubility, mg/mLb (Na salt) |
|---|---|---|---|---|---|---|---|---|
| 75 | N | CH | CH | 12.9 | >200 | 113.7 | 16.1 | N/D |
| 76 | CH | N | CH | 2.67 (0.06) | >200 | 54.0 | 6.7 | 2.4 (16.9) |
| 77 | CH | CH | N | 3.4 | 180 | 23.4 | 1.8 | ND |
| 62 | CH | CH | CH | 4.5 (0.125) | >200 | 58.2 | 6.2 | 1.1 (18.9) |
a
NDM-1-producing strain E. coli NTBC121 (MEM MIC, 32 μg/mL). The inhibitor was present at 100 μM.
b
Solubility was determined in phosphate-buffered saline (PBS) at pH 7.4.