Fig 3.

(A) Morphological changes in P. falciparum parasites seen over a 48-h period when treated with 5 μM CHR-2863 compared to an untreated control and a known cysteine protease inhibitor, E64. (B) Mice infected with P. c. chabaudi parasites were dosed by oral gavage with a range of concentrations of CHR-2863. Five groups of mice were used: (i) a no-drug vehicle control group, (ii) a group given one daily dose of 100 mg/kg of CHR-2863 on days 1 and 2 followed by one daily dose of 50 mg/kg on days 3 and 4, (iii) a group given one daily dose of 50 mg/kg of CHR-2863 on days 1 to 4, (iv) a group given one daily dose of 25 mg/kg of CHR-2863 on days 1 to 4, and (v) a group given a daily dose of 14 mg/kg malarone (atovaquone at 10 mg/kg plus proguanil at 4 mg/kg) on days 1 to 3. Each mouse received 1 × 10⁵ P. c. chabaudi parasites intravenously on day 0, and all compounds, including the vehicle control, were administered by oral gavage in a total volume of 200 μl. Dosing of the animals commenced 24 h after inoculation of parasites and was repeated at 24-h intervals. Peak parasitemia corresponds to the percentage of parasitized red blood cells quantified from Giemsa-stained thin films. The doses on the x axis correspond to the amount of CHR-2863 given per day over 4 days in mg/kg. A black horizontal line indicates the mean parasitemia of each of the test and control groups. **, P < 0.01; ***, P < 0.001.