Table 1.
Effective concentration (EC) in µM of 25 di-substituted urea compounds against T. cruzi epimastigotes and LLC-MK2 cells.
Compound | T. cruzi epimastigotesa | LLC-MK2b EC50 (μM) | Selectivity Indexc (SI) | |
---|---|---|---|---|
EC50 (μM) | EC90 (μM) | |||
3p | 1.3d | 4.4d | 7.7 ± 3.7 | 5.9 |
6a | 1.7 ± 0.1 | 7.5 ± 0.5 | 13.7 ± 8.7 | 8.0 |
I-17 | 3.4 ± 1.3 | 5.7 ± 1.5 | 32.4 ± 14.7 | 9.5 |
3e | 2.3d | 2.8d | 6.6 ± 3.6 | 1.4 |
6b | 2.5 ± 0.4 | 4.6 ± 0.1 | 2.5 ± 0.4 | 1.0 |
I-18 | 3 ± 0.7 | 6.6 ± 1.8 | 12.3 ± 8.8 | 4.1 |
3 g | 3.3 ± 0.1 | 8.4 ± 2.4 | 7 ± 4.7 | 2.1 |
3r | 3.5 ± 0.1 | 6 ± 0.9 | 8.6 ± 1.2 | 2.4 |
3q | 3.7 ± 2.5 | 8.7 ± 1.0 | 1.2 ± 1.3 | 0.7 |
3 f | 5.4 ± 0.2 | 16.8 ± 5.5 | N.T.f | N.T. |
3o | 5.5 ± 0.4 | 7.3 ± 0.8 | N.T. | N.T. |
3 m | 5.9 ± 0.3 | 7.7 ± 0.1 | N.T. | N.T. |
3i | 6.3 ± 0.5 | 12.1 ± 1.7 | N.T. | N.T. |
I-m6 | 6.5 ± 0.2 | 10.4 ± 0.8 | N.T. | N.T. |
3a | 7.7 ± 0.5 | 9.9 ± 0.3 | N.T. | N.T. |
3c | 7.7 ± 0.4 | 9.7 ± 0.4 | N.T. | N.T. |
3 h | 8.2 ± 0.1 | 13.5 ± 4.5 | N.T. | N.T. |
3b | >10g | >10 | N.T. | N.T. |
3n | >10 | >10 | N.T. | N.T. |
3d | >10 | >10 | N.T. | N.T. |
3j | >10 | >10 | N.T. | N.T. |
3k | >10 | >10 | N.T. | N.T. |
3 l | >10 | >10 | N.T. | N.T. |
3t | >10 | >10 | N.T. | N.T. |
NCPdCPU | >10 | >10 | N.T. | N.T. |
BZNe | 211 ± 3.0 | 960 ± 25.0 | N.T. | N.T. |
aEpimastigotes of T. cruzi were incubated for 3 days in the presence of different concentrations of each compound in triplicate experiments, each value determined in duplicate measurements. The concentration that inhibited 50% (EC50) or 90% (EC90) of multiplication was determined by using the Alamar Blue assay as described in Methods.
bLLC-MK2 were plated and after 24 h, incubated with the different concentrations of the indicated compounds. After two more days, cell viability was measured with Alamar Blue assay as described in Methods and the results used to determine the (EC50).
cTI = Ratio between T. cruzi EC50 and LLC-MK2 EC50.
dThese values correspond to a single experiment.
eBZN = Benznidazole.
fN.T. = not tested.
g>10 = without apparent effect at 10 µM.