Table 9. Inhibition of DprE1 and Cellular Potency by Thiophene-arylamides.
| compounds | MICOE (μg/mL)a (DprE1) | MICOE (μg/mL)b (DprE2) | MICWT (μg/mL)c | MIC foldshiftd | IC50 DprE1 (μg/mL)e |
|---|---|---|---|---|---|
| 23j | >1.28 | 0.32 | 0.32 | >4 | 0.3 ± 0.1 |
| 24f | >0.51 | 0.13 | 0.064 | >8 | 0.2 ± 0.04 |
| 24j | 8.96 | 0.56 | 0.28 | 32 | 0.3 ± 0.1 |
| 25a | >12.16 | 1.52 | 0.76 | >16 | 0.9 ± 0.2 |
| 25b | >1.98 | 0.25 | 0.12 | >16 | 0.4 ± 0.1 |
| 25l | 12.8 | 1.60 | 1.60 | 8 | 0.4 ± 0.1 |
| TCA1 | 15.36 | 0.96 | 0.48 | 32 | 0.1 ± 0.01 |
a
Overexpressor (OE) MICs are for Mycobacterium bovis bacillus Calmette-Guerin (BCG) Pasteur transformed with pMV261:Mt-dprE1.
b
Overexpressor (OE) MICs are for M. bovis BCG Pasteur transformed with pMV261:Mt-dprE2.
c
MICs against M. bovis BCG Pasteur strain transformed with pMV261.
d
Ratio of MIC values against the DprE1-overexpressing strain and wild-type strain.
e
All in vitro assays were performed using Mt-DprE1.