Table 1. In Vitro Activity of 3-Br-isoxazoline-Based Inhibitors against Plasmodium falciparum (D10 and W2 strains) and Leishmania spp. (L. infantum and L. tropica) Promastigotes.
| compd | P. falciparum D10 IC50 (μM)a | P. falciparum W2 IC50 (μM)a | L. infantum IC50 (μM)b | L. tropica IC50 (μM)b |
|---|---|---|---|---|
| 3 | 0.37 ± 0.12 | 0.26 ± 0.05 | n.d. | n.d. |
| 4 | 0.36 ± 0.11 | 0.48 ± 0.18 | n.d. | n.d. |
| 5 | inactivec | inactivec | n.d. | n.d. |
| 6a | 52.7 ± 14.4 | 64.8 ± 9.5 | 17.3 ± 7.4 | 43.0 ± 22.6 |
| 6b | 52.7 ± 14.2 | 46.0 ± 3.5 | 26.2 ± 13.1 | 24.9 ± 8.26 |
| 6c | 58.3 ± 8.1 | 48.1 ± 0.1 | 27.3 ± 12.3 | 32.6 ± 12.7 |
| 6d | inactivec | inactivec | 9.0 ± 2.7 | 10.9 ± 2.8 |
| 6e | 31.0 ± 6.9 | 34.0 ± 14.8 | 8.7 ± 4.5 | 6.9 ± 2.6 |
| 6f | 3.1 ± 0.1 | 3.5 ± 0.4 | 0.29 ± 0.11 | 0.31 ± 0.03 |
| 6g | 34.4 ± 5.8 | 42.5 ± 6.0 | 12.0 ± 2.0 | 14.7 ± 8.1 |
| 6h | 29.8 ± 4.5 | 32.7 ± 2.8 | 25.6 ± 6.2 | 39.4 ± 11.8 |
| 6i | 27.8 ± 1.1 | 27.2 ± 1.5 | 10.5 ± 4.4 | 5.3 ± 2.8 |
| 6j | 36.9 ± 5.0 | 45.3 ± 4.8 | inactivec | inactivec |
| 6k | 45.9 ± 7.5 | 40.4 ± 13.0 | inactivec | inactivec |
| 6l | 45.7 ± 12.2 | 39.5 ± 17.0 | 28.8 ± 5.0 | 33.8 ± 24.2 |
| 6m | 39.0 ± 16.3 | 32.5 ± 12.9 | 14.7 ± 6.16 | 25.6 ± 11.7 |
| 7 | 16.7 ± 8.3 | 15.1 ± 7.6 | inactivec | inactivec |
| 8 | 35.3 ± 15.9 | 43.0 ± 7.1 | inactivec | inactivec |
| 9 | 32.2 ± 14.7 | 39.3 ± 11.8 | inactivec | 50.7 ± 20.1 |
| 10 | 22.9 ± 9.6 | 41.3 ± 8.8 | 60.3 ± 6.2 | inactivec |
| 11 | 45.8 ± 3.9 | 39.7 ± 3.9 | 28.8 ± 5.0 | 33.8 ± 24.2 |
| 12 | 0.035 ± 0.014 | 0.058 ± 0.014 | 3.5 ± 1.2 | 7.5 ± 3.4 |
| CQ | 0.028 ± 0.004 | 0.406 ± 0.113 | n.d. | n.d. |
| AMB | n.d. | n.d. | 0.11 ± 0.02 | 0.12 ± 0.02 |
a
pLDH method; data are the mean of three different experiments ± SD; D10: CQ-susceptible Pf strain; W2: CQ-resistant Pf strain; n.d.: not determined.
b
MTT assay; data are the mean of three different experiments ± SD; n.d.: not determined.
c
No activity observed at the highest concentration tested (60 μM).