Table 1. Sensitivity of WT, (R)-PA-824 resistant and transgenic L. donovani promastigotes to nitroheterocyclic compounds.
| Nitroheterocyclic compounds EC50 values, nM (slope factor) a | ||||||||
|---|---|---|---|---|---|---|---|---|
| Cell line | (R)-PA-824 | (S)-PA-824 | Delamanid | (S)-OPC 67683 | DNDI-VL-2098 | CGI-17341 | Fexinidazole sulfone | Nifurtimox |
| WT | 93.6 ± 2.0 (3.5) | 2567 ± 50 (3.5) | 15.5 ± 0.1 (6.7) | 146.9 ± 4.1 (2.9) | 30.8 ± 2.8 (1.7) | 30.6 ± 1.1 (10.7) | 8,200 ± 101 (3.1) | 1,800 ± 40 (3.2) |
| RES III | >100,000 | >50,000 | >50,000 | >50,000 | >50,000 | >20,000 | 8,900 ± 130 (3.1) | 6,020 ± 32 (2.6) |
| NTR2 OE | 8.7 ± 0.3 (2.0) | 95 ± 1.6 (2.2) | 0.8 ± 0.03 (4.2) | 48 ± 3.0 (2.7) | 5.4 ± 0.38 (2.4) | 1.9 ± 0.1 (8.9) | 4600 ± 30 (2.7) | 122 ± 8.2 (2.8) |
| NTR2 DKO | >100,000 | >50,000 | >50,000 | N.D. | >50,000 | N.D. | 7,880 ± 70 (3.2) | 6,400 ± 70 (2.8) |
a Data are the weighted means and weighted standard errors of 3 independent experiments. Each individual experiment is derived from a 10 point dilution curve, where each individual sample is measured in triplicate.
N.D–not determined