FIG 4.

In vivo activity of selected modified nitrothiazoles in murine giardiasis. (A) Structures of the six representative nitrothiazoles that were selected for further tests, resynthesized, and purified to >90%. (B) In vitro activity of the depicted compounds against G. lamblia strain GS/M (a human-pathogenic strain belonging to assemblage B) was determined in a 48-h growth and survival assay. Data are shown as individual pEC50 values of three independent experiments, with metronidazole (Mz) shown as a reference drug. Mean pEC50 values that were significantly different (P < 0.05) from those for metronidazole are indicated by an asterisk. (C) The six compounds and Mz were subsequently tested for in vivo efficacy in mice infected with the G. lamblia strain GS/M. Two days after infection, compounds were orally administered to mice in two daily doses of 10 mg/kg for a total of 5 doses over a 3-day period or the mice were given solvent alone as controls, and trophozoite numbers in the small intestine were determined. Data are shown as individual log₁₀-transformed counts with six to eight animals in each group. Horizontal lines depict the geometric mean for each group. The gray zone represents the 95% confidence interval of the counts in the controls.