TABLE 3.
Activity of hits from validation screens against asexual-stage P. falciparum parasitesa
| Cluster | Sample identifier | cLogPb | % growth inhibition at 5 μM | EC50c (μM) |
||||
|---|---|---|---|---|---|---|---|---|
| P. falciparum 3D7 | HeLa cells | HEK293 cells | IMR90 cells | L. amazonensis promastigotes | ||||
| Cluster 1, aporphines | NCGC00162155 | 1.82 | 48.38 ± 1.44 | 4.1 ± 0.18 | 19.0 ± 6.1 | >25 | >25 | 19.4 ± 0.8 |
| NCGC00025349 | 2.49 | 47.1 ± 6.28 | 1.3 ± 0.1 | >25 | >25 | >25 | 7.32 ± 0.3 | |
| NCGC00162160 | 2.88 | 17.88 ± 2.67 | 11.6 ± 1.7 | >25 | >25 | 10.7 ± 0.1 | ||
| Cluster 2, benzazepines | NCGC00162096 | 4.32 | 51.41 ± 1.44 | 31 ± 6.4 | >25 | >25 | >25 | 13.1 ± 0.6 |
| NCGC00015186 | 4.12 | 38.03 ± 1.57 | >25 | 24.8 ± 0.1 | >25 | 21.3 ± 3.1 | ||
| Cluster 4, tetrahydrobenzothiophenes | NCGC00098819 | 5.69 | 12.64 ± 1.75 | 5.3 ± 2 | 15.4 ± 0.9 | 3.1 ± 1.4 | >25 | |
| NCGC00098559 | 5.87 | 13.2 ± 1.11 | 4.7 ± 1.4 | 2.8 ± 0.3 | 7.2 ± 1.5 | >25 | ||
| NCGC00098561 | 5.87 | 27.18 ± 2.19 | 2.7 ± 1.1 | 2.7 ± 0.5 | 5.4 ± 1.2 | >25 | ||
| Singletons | NCGC00099116 | 4.38 | 10.53 ± 1.84 | >25 | 10.3 ± 1.1 | >25 | 22.2 ± 0.8 | |
| NCGC00346707 | 3.49 | 80.97 ± 0.63 | 5.1 ± 0.17 | >25 | 5.2 ± 0.6 | >25 | 6.3 ± 0.04 | |
| NCGC00163250 | 4.13 | 80.14 ± 1.75 | 1.7 ± 0.22 | >25 | 10.0 ± 3.4 | >25 | >25 | |
| NCGC00094456 | 5.38 | 87.62 ± 0.87 | 1.9 ± 0.14 | 12 ± 0.5 | 7.3 ± 1.0 | 17.6 ± 3.6 | 2.3 ± 0.1 | |
| NCGC00162149 | −0.58 | 29.69 ± 2.31 | >25 | >25 | >25 | 16.4 ± 3.5 | ||
| NCGC00250410 | 5.67 | 91.12 ± 0.33 | 0.78 ± 0.04 | 12.8 ± 4.2 | >25 | >25 | 20.1 ± 5 | |
| NCGC00262398 | 5.02 | 23.42 ± 1.13 | 10.1 ± 0.2 | 8.5 ± 1.7 | 23.6 ± 1.5 | 21.5 ± 2.7 | ||
| NCGC00018296 | 6.73 | 52.19 ± 2.48 | 5.0 ± 0.41 | >25 | >25 | >25 | 3.5 ± 0.7 | |
| NCGC00242503 | 5.52 | 15.01 ± 5.17 | >25 | 24.3 ± 1.0 | >25 | 12.1 ± 0.3 | ||
| NCGC00016069 | 1.49 | 11.47 ± 3.49 | >25 | >25 | >25 | >25 | ||
a
Only compounds that inhibited P. falciparum growth by more than 10% at 5 μM are included.
b
cLogP values were calculated using ChemBridge software.
c
P. falciparum dose-response curves for compounds that caused >45% growth inhibition at 10 μM were performed in duplicate, and averages were used to resolve EC50s. All human cell lines were evaluated in three independent experiments.