TABLE 4.
MICs of PAINS analogs against E. coli ΔtolC tmk(A69T) and plasmid-overexpressing strains, as well as IC50 values for the inhibition of E. coli TMPK in vitro
| Compounda | Allele-conferred resistance (μM) |
Plasmid overexpression (μM) |
In vitro inhibition (μM) |
|||||
|---|---|---|---|---|---|---|---|---|
|
E. coli
ΔtolC tmk + |
E. coli ΔtolC tmk(A69T) |
Conferred fold resistance |
Vector control |
Plasmid+ tmk |
Plasmid+ tmk(Q45P) |
Plasmid+ tmk(A69T) |
E. coli TMPK IC50 | |
| 1 | 11.7 | 68.8 | 5.9 | 15.5 | 62 | 62 | 62 | 0.39 |
| 2 | 6.1 | 14.8 | 2.4 | 7.8 | 31 | 62 | 62 | 2.50 |
| 8a | >100 | 1.20 | ||||||
| 9 | 11.7 | 43.8 | 3.7 | 15.5 | 62 | 62 | 62 | 0.41 |
| 11 | 14.1 | 37.5 | 2.7 | 15.5 | 62 | >62 | >62 | 0.48 |
| 12 | 9.0 | 20.3 | 2.3 | 7.8 | 31 | >62 | >62 | 0.50 |
| 13 | 28.1 | 56.3 | 2.0 | 31.3 | 62.5 | 62.5 | 62.5 | 1.00 |
| 14* | >100 | 4.20 | ||||||
| 16* | >100 | 5.60 | ||||||
| 27 | 1.9 | 18.8 | 10 | 3.9 | 15.5 | 15.5 | 15.5 | 0.25 |
| 28 | 7.8 | 19.4 | 2.5 | 7.8 | 31.3 | 64 | 64 | 0.47 |
| 31 | 43.7 | 93.8 | 2.1 | 31.3 | 125 | 125 | 125 | 0.68 |
a
*, inactive in vivo.