Table 1.
Correlation between inhibition on DprE1 WT and mutant enzyme activity and cellular potency by TCA1 and analogs (μm).4d
| TCA1 analogs | IC50 DprE1 WT[a] | IC50 DprE1 Y321C[a] | MIC WT | MIC Y314C |
|---|---|---|---|---|
| TCA1 | 0.048±0.014 | 0.24±0.052 | 0.23±0.012 | 5.4±0.32 |
| TCA007 | 0.0053±0.18 | 0.13±0.021 | 0.089±0.0066 | 2.4±0.34 |
| TCA481 | ND[b] | ND[b] | 0.046±0.0025 | 1.4±0.086 |
| TCA020 | 0.37±0.13 | >10 | 2.5±0.48 | 17±1.1 |
| TCA787 | 0.096±0.038 | 1.8±0.54 | 0.44±0.12 | 14±1.4 |
[a] All in vitro assays were performed using M. smegmatis DprE1 which shows 83 % sequence identity with Mtb DprE1. M. smegmatis Y321C corresponds to Y314C in Mtb. [b] IC50 of TCA481 was not determined due to its low solubility under the assay condition.