In Vitro Activity of Geldanamycin Derivatives against Schistosoma japonicum and Brugia malayi
Figure 3
(a) Effect of Geldanamycin and 17-AAG on adult Brugia malayi in vitro. 17-AAG killed B. malayi adults faster and at concentrations two hundred times lower than albendazole (positive control). Statistically significant differences in rates of killing were observed for 5–100 μM GA and 17-AAG versus 100 μM albendazole (positive control, ). 500 nM and 1000 nM GA and 17-AAG were equivalent to 100 μM albendazole at 280–300 hours. (b) Effect of 17-AAG compared to three other GA derivatives on adult B. malayi in vitro. Negative control worms (i.e., no drug) remain viable for 500 hours and 100 μM albendazole kills parasites by 15 days. All three concentrations of the four GA derivatives killed adult B. malayi faster than 100 μM albendazole (positive control, ). Numbers above each bar are mean hours to 100% killing. Compounds 3 (DMAG) and 5 (5′-bromogeldanoxazinone) were more active against B. malayi than 17-AAG at 500 nM (). All four compounds at each concentration tested (500 nM—10 μM) killed filarial more quickly than 100 μM albendazole (positive control, ). For (a) and (b), the data represent the mean ± S.D. of triplicate determinations in a representative experiment.
