Table 1.
Structures and IC50s in the yeast and parasite growth and [3H]adenosine uptake assays for the nine compounds selected from the HTS.
| HTS Rank # |
Structure | Compound Name ChemBridge # |
EC50 5-FUrd growth rescue of fui1Δ::Pf ENT1- HA-CO (µM) |
IC50 ade2Δ + PfENT1- CO adenosine growth inhibition (µM) |
IC50 [3H]- adenosine uptake into ade2Δ + PfENT1- CO yeast (nM) |
IC50 [3H]- adenosine uptake into 3D7 parasites (nM) |
IC50 3D7 parasite viability – low purine media (µM) |
IC50 3D7 parasite viability – high purine media (µM) |
IC50 Dd2 parasite viability – high purine media (µM) |
|---|---|---|---|---|---|---|---|---|---|
| 1 |  |
N,N'-1,3- benzothiazole-2,6- diyldi(2-furamide) 9001893 |
0.8 ± 0.0 |
0.2 ± 0.1 |
3.0 ± 1.3 |
5.4 ± 2.9 |
31.1 ± 4.7 |
37.7 ± 2.0 |
25.8 ± 1.3 |
| 2 |  |
2-bromo-N-(4- [1,3]oxazolo[4,5- b]pyridin-2- ylphenyl)benzamide 6718896 |
6.0 ± 1.7 |
2.1 ± 0.9 |
10.1 ± 8.4 |
28.0 ± 12.3 |
31.2 ± 7.7 |
53.4 ± 11.1 |
52.4 ± 5.7 |
| 3 |  |
4-methyl-7-[(3,4,5- trimethoxybenzyl)oxy] -2H-chromen-2-one 6946484 |
2.3 ± 0.9 |
0.6 ± 0.1 |
2.4 ± 1.5 |
6.4 ± 3.0 |
19.2 ± 4.3 |
41.0 ± 4.3 |
36.2 ± 6.0 |
| 4 |  |
N-{4-[5-(2-furyl)-1,3,4- oxadiazol-2- yl]phenyl}-2-furamide 6081106 |
5.7 ± 0.8 |
1.7 ± 0.4 |
13.7 ± 7.5 |
45.8 ± 24.1 |
15.0 ± 1.5 |
14.7 ± 1.9 |
15.3 ± 2.7 |
| 5 |  |
2-(1-methyl-1H-indol- 3-yl)-2-oxo-N-[4- (pyrrolidin-1- ylcarbonyl)phenyl]acet amide 9039333 |
6.5 ± 1.5 |
2.0 ± 0.01 |
22.7 ± 7.2 |
38.6 ± 20.1 |
35.5 ± 0.7 |
33.1 ± 0.5 |
28.9 ± 2.6 |
| 6 |  |
3-fluoro-N-(3- [1,3]oxazolo[4,5- b]pyridin-2- ylphenyl)benzamide 9011026 |
5.7 ± 1.3 |
1.1 ± 0.1 |
9.6 ± 7.4 |
19.8 ± 12.9 |
34.8 ± 2.4 |
33.7 ± 5.0 |
38.8 ± 4.9 |
| 7 |  |
2-methoxy-N-(3- [1,3]oxazolo[4,5- b]pyridin-2- ylphenyl)benzamide 6736283 |
6.4 ± 0.9 |
1.6 ± 0.01 |
10.9 ± 6.8 |
24.8 ± 17.4 |
43.6 ± 4.4 |
44.8 ± 3.8 |
31.0 ± 0.6 |
| 13 |  |
2-[2-(2- methylphenyl)vinyl]- 4(3H)-quinazolinone 6517398 |
4.7 ± 2.9 |
0.6 ± 0.1 |
3.9 ± 1.6 |
21.6 ± 14.2 |
6.9 ± 0.4 |
6.7 ± 0.5 |
2.6 ± 0.2 |
| 19 |  |
N-(4-chloro-3- [1,3]oxazolo[4,5- b]pyridin-2-ylphenyl)- 2- thiophenecarboxamid e 9011680 |
5.4 ± 0.8 |
1.7 ± 0.2 |
38.4 ± 16.5 |
17.9 ± 12.7 |
43.2 ± 2.9 |
42.9 ± 2.8 |
37.4 ± 1.6 |
Mean ± SD are shown, N ≥ 3 biological replicates for all data.
HTS Rank # from SI Table S2 based on efficacy in the primary HTS.