TABLE 1.
In vitro antiprotozoal and cytotoxic activity of STLs determined for this study and not previously published
| Compound | IC50 (μM)a |
||||
|---|---|---|---|---|---|
| T. brucei rhodesiense | T. cruzi | L. donovani | P. falciparum | Cytotoxicity (L6 myoblasts) | |
| 41 | 3.56 ± 1.69 | 13.7 ± 0.9 | 9.33 ± 1.78 | 2.91 ± 0.27b | 10.7 ± 4.0 |
| 42 | 24.4 ± 2.9 | 78.3 ± 16.4 | 22.9 ± 0.71 | 22.2 ± 1.9b | 53.3 ± 12.7 |
| 43 | 24.6 ± 1.4 | 106.4 ± 27.3 | 50.8 ± 0.6 | 25.4 ± 1.6b | 58.9 ± 8.6 |
| 44 | 13.3 ± 5.8 | 40.1 ± 12.8 | 7.67 ± 0.36 | 18.0 ± 1.5b | 22.5 ± 5.6 |
| 45 | 1.98 ± 0.29 | 17.6 ± 2.8 | 2.13 ± 0.36 | 12.1 ± 1.8b | 7.20 ± 0.46 |
| 49 | 2.52 ± 0.42 | 18.9 ± 2.0 | 2.49 ± 0.13 | 7.38 ± 1.04c | 6.18 ± 0.28 |
| 52 | 234.5d | 254.7 ± 67.2 | >400e | 196.0 ± 7.3 | >400e |
| 55 | 2.03 ± 0.26 | 27.7 ± 6.4 | 4.17 ± 0.61 | 6.29 ± 0.09b | 15.5 ± 0.4 |
| 57 | 4.31 ± 2.29 | 13.8 ± 2.2 | 6.39 ± 0.62 | 7.71 ± 0.22b | 5.30 ± 1.40 |
| 62 | 0.227 ± 0.002 | 10.8 ± 2.8 | 4.72 ± 0.71 | 8.26 ± 0.62b | 4.70 ± 0.90 |
| 63 | 2.46 ± 0.27 | 22.1 ± 0.7 | 21.9 ± 1.6 | 4.53 ± 0.69c | 7.64 ± 0.35 |
| 65 | 2.08 ± 0.09 | 11.3 ± 3.3 | 2.69 ± 1.08 | 3.12 ± 0.52c | 4.91 ± 0.53 |
| 70f | 0.073 ± 0.002 | 1.08 ± 0.10 | 0.448 ± 0.021 | 0.291 ± 0.158b | 0.494 ± 0.086 |
| 71f | 0.072 ± 0.0006 | 1.75 ± 0.01 | 5.14 ± 0.21 | 1.24 ± 0.33c | 0.384 ± 0.020 |
| 72f | 0.202 ± 0.005 | 2.13 ± 0.30 | 0.518 ± 0.053 | 2.03 ± 0.53c | 4.31 ± 0.17 |
| 73f | 0.015 ± 0.003 | 3.74 ± 1.34 | NA | 1.03 ± 0.24c | 1.15 ± 0.53 |
| Positive controls | 0.006 ± 0.002g | 1.68 ± 0.31h | 0.411 ± 0.068i | 0.241 ± 0.025b,j; 0.008 ± 0.002c,j | 0.016 ± 0.004k |
Each entry is the mean of two independent measurements ± the deviation of the minimum and maximum values. For the positive controls, data are means of 3 to 8 independent measurements ± standard deviations. The data for anti-T. b. rhodesiense activity were used together with those of compounds 1 to 40, 46 to 48, 50, 51, 53, 54, 56, 58 to 61, 64, and 66 to 69 in the current QSAR analysis. A full list with the pIC50 data of all compounds against T. b. rhodesiense is presented in Table SA1 in the supplemental material. NA, data for the axenic amastigote model were not available (inactive at 3 μg/ml against intracellular amastigotes).
Strain K1.
strain NF54.
Only one definite measurement of IC50 was obtained; the second measurement yielded an IC50 of >400 μM.
Highest concentration tested; IC50 was not determined.
Compound selected for testing after QSAR-based prediction of anti-T. b. rhodesiense activity.
Melarsoprol.
Benznidazole.
Miltefosine.
Chloroquine.
Podophyllotoxin.