Table 1. Inhibitory Activity of Bacterial Phosphotransferases (MraY and WecA) and C. difficile Growth by the C5′- and 6′-Diastereomers of FR-900493a.
| compound | WecA inhibition IC50(μM)b | MraY inhibition IC50 (μM)c | C. difficile ATCC 43596 MIC (μg/mL)d |
|---|---|---|---|
| FR-900493 (1) | 5.0 ± 5.44 | 25.0 ± 8.67 | >25.0 |
| 5′S,6′R-diastereomer (4) | >100 | >100 | >25.0 |
| 5′R,6′S-diastereomer (5) | >100 | >100 | >25.0 |
| 5′R,6′R-diastereomer (6) | >100 | >100 | >25.0 |
| FR-900493-amide (7) | 5.0 ± 6.34 | 25.0 ± 9.67 | >25.0 |
| 8 | >100 | >100 | >25.0 |
| tunicamycin | 0.15 ± 7.80 | 3.38 ± 7.32 | >25.0 |
a
WecA and MraY assays (see the Supporting Information).
b
E. coli WecA-containing membrane was used.
c
Hydrogenivirga spp. MraY was used.
d
A microdilution broth method was used.