Figure 5. Cellular activity of compounds with good potency in the extracellular but varying potency in the intracellular model.

All three compounds tested showed cellular activity on the intracellular and extracellular L. donovani amastigotes. When tested against intracellular amastigotes, only DDD100887 generated a reproducible dose-response curve. It was not possible to generate dose-response curves for DDD85646 and DDD86211 as both compounds resulted in an reproducible “activity valley” at higher concentrations before resulting in complete killing of the parasites at the highest concentration tested (see text for details). One representative experiment is shown for each compound. The correlation coefficients for the extracellular amastigotes were R²>0.98, with almost all very close to or >0.99. The correlation coefficient for intracellular DDD100887 is R² 0.9212.