TABLE 4.
Compound | Mean EC50 (μM) ± SD (RI [EC50 decrease]) |
|
---|---|---|
pUCNEO | LABCG2 | |
SbIII | 6.50 ± 1.01 | 37.45 ± 1.50 (5.8)† |
SbIII + BSO | 4.96 ± 1.23 (1.3) | 8.23 ± 0.91 (1.7 [4.5])* |
Parasites were grown in M199 culture medium supplemented with 10% hiFBS for 72 h at 28°C in the presence of increasing concentrations of SbIII. Cell viability was determined by using an MTT-based assay as described in Materials and Methods. Resistance indexes (RI), indicated in parentheses, were calculated by dividing the EC50 for the Leishmania line overexpressing LABCG2 by that for the Leishmania control line (pUCNEO) with the same treatment. The EC50 decrease, indicated in square brackets, was calculated by dividing the EC50 after SbIII treatment by that for treatment with SbIII plus BSO (a γ-glutamylcysteine synthetase inhibitor) in each Leishmania line. A total of 3 mM BSO was added to the culture medium 48 h before the susceptibility experiment was performed. The data are the means ± standard deviations of results from three independent experiments. Significant differences were determined by the Student t test (†, P < 0.01 for pUCNEO versus the LABCG2 line; *, P < 0.01 for the LABCG2 line treated with versus without BSO).