TABLE 5.
Comparison of in vitro extracellular promastigote susceptibility to the selected AP series before and after in vivo passage (mouse and sandfly) between the wild type and the generated clones
| Time relative to passage | Compound | Mean IC50 (μM) ± SEMa |
||
|---|---|---|---|---|
| Wild type | LEM3323Cl4/1044Cl1 | LEM3323Cl4/8012Cl2 | ||
| Original | DNDI-1044 | 0.46 ± 0.05 | 3.37 ± 0.54 (7.3)**** | 2.63 ± 0.25 (5.7)*** |
| DNDI-8012 | 0.66 ± 0.09 | 4.12 ± 0.89 (6.2)**** | 3.81 ± 0.43 (5.7)**** | |
| DNDI-5561 | 0.80 ± 0.08 | 9.28 ± 1.01 (11) | 7.68 ± 1.09 (9.6)* | |
| After mouse passage | DNDI-1044 | 0.61 ± 0.09 | 0.64 ± 0.10 (1.0) | 1.86 ± 0.15 (3.0) |
| DNDI-8012 | 0.73 ± 0.15 | 1.01 ± 0.06 (1.4) | 2.68 ± 0.29 (3.7) | |
| DNDI-5561 | 0.68 ± 0.05 | 0.95 ± 0.16 (1.4) | 2.18 ± 0.54 (3.2) | |
| After sandfly passage | DNDI-1044 | 0.51 ± 0.07 | 0.55 ± 0.10 (1.1) | 1.36 ± 0.27 (2.6) |
| DNDI-8012 | 0.78 ± 0.12 | 0.85 ± 0.13 (1.1) | 1.76 ± 0.17 (2.2)* | |
| DNDI-5561 | 0.74 ± 0.08 | 0.76 ± 0.07 (1.0) | 1.20 ± 0.39 (1.6) | |
a
Results are based on three independent replicates run in duplicate. The resistance index (RI) is given in parentheses and was always calculated with respect to the corresponding wild type. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001.