Fig 2.

In vitro BLI analysis of the activity of ICI 56,780, P4Q-146, and P4Q-158 against Plasmodium berghei liver stage parasites. HepG2 cells (75,000 per well) were infected with Pb1052 Cl1 sporozoites (5,000 per well). The infected cells were treated with a series of eight 3-fold dilutions of each compound in triplicate. Concentrations started at 50 ng/ml for both P4Q-146 and P4Q-158, 1 ng/ml for ICI 56,780, and 20 ng/ml for atovaquone. At 44 h postexposure, plates were analyzed using the Xenogen IVIS spectrum. (A) All of the compounds with the exception of chloroquine (CQ) were active against Plasmodium berghei parasites in vitro. IC₅₀s for ICI 56,780, P4Q-146, and P4Q-158 were 0.08, 2.82, and 3.07 nM, respectively. As expected, atovaquone (ATOV; positive drug control) was active against the liver stage parasites with an IC₅₀ of 1.42 nM. Infected but untreated cells were used as a positive control (P), and noninfected HepG2 cells were used as a negative control (N). (B to E) Sigmoidal plots used to obtain IC₅₀s from the Xenogen IVIS spectrum and luminometer data for atovaquone (B), ICI 56,780 (C), P4Q-146 (D), and P4Q-158 (E) are shown.