Table 3.
IC50 values on NTS and adult S. mansoni, toxicity on L6 and MRC5-cells and selectivity of the 11 Stasis Box lead molecules. Cytotoxic concentration (CC50) and selectivity index (SI) are compared to the mean IC50 values measured on NTS and adult S. mansoni in standard and albumin-enriched medium (45 g/l) over 72 h with 11 Stasis Box lead compounds
| Compound MMV ID |
NTS IC50 (μM)a | Adult IC50 (μM)a | Adult IC50 (μM) with albumina | L6 cells | MRC5 cellsd | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 24 h | 48 h | 72 h | 24 h | 48 h | 72 h | 24 h | 48 h | 72 h | CC50 (μM) | SI | CC50 (μM) | SI | |
| MMV690732 | 29.5 | 6.3 | 3.5 | 4.9 | 2.9 | 2.5 | 62.8 | 181.0 | 54.1 | 2.3 | 0.9 | 1.9 | 0.7 |
| MMV690596 | 1.1 | 1.3 | 0.6 | 1.0 | 2.1 | 2.0 | 27.5 | 14.4 | 11.0 | 3.5 | 1.7 | 1.9 | 0.9 |
| MMV003452 | 4.4 | 2.2 | 1.2 | 1.7 | 3.0 | 2.7 | 22.6 | 12.0 | 7.5 | 3.7 | 1.4 | 1.9 | 0.7 |
| MMV690599 | 10.5 | 3.5 | 1.5 | 2.5 | 3.3 | 2.6 | 23.6 | 19.1 | 15.9 | 3.4 | 1.3 | 2 | 0.8 |
| MMV690466 | 14.6 | 3.8 | 2.1 | 2.9 | 2.3 | 2.0 | 18.1b | 89.7 | 47.6 | 1.6 | 0.8 | 8.4 | 4.3 |
| MMV690787 | 38.4b | 8.1 | 6.3 | 7.9 | 7.2 | 3.1 | 39.5 | 14.4 | 13.3 | na | na | 0.1 | 0 |
| MMV690684 | 4.0c | 3.1c | 0.7 | 4.9 | 4.7 | 3.7 | 76.8 | 14.4b | 7.7 | 7.0 | 1.9 | 7 | 1.9 |
| MMV690646 | 3.0c | 1.1 | 0.9 | 3.7 | 2.2 | 2.2 | 32.0 | 121.8 | 33.6 | na | na | 0.2 | 0.1 |
| MMV690765 | 914.4b | > 1c | 0.5b | 4.2 | 3.4 | 2.9 | 651.7 | 225.9b | 123.5b | 11.8 | 4.1 | 0.7 | 0.3 |
| MMV690534 | 11.8 | 14.3c | 7.2c | 17.4 | 19.3 | 7.5 | na | na | na | 74.5 | 15.0 | 12.4 | 2.5 |
| MMV001539 | 12.7 | 11.0c | 1.7 | 28.2 | 12.3 | 7.0 | nd | nd | nd | 2.9 | 0.4 | 16 | 2.1 |
Abbreviations: na not applicable. nd not done
ar-values ranged between 0.7 and 1.0
bThese values are based on one replicate only because of an r-value < 0.70 was obtained for the second replicate
cThe IC50 values obtained in each of the two replicate differed more than 5.5-fold
dThe CC50 values on MRC5 cells were provided by MMV