In vivo efficacy of beta-cyclodextrin derivatives against anthrax lethal toxin

Abstract

We evaluated the in vivo efficacy of three beta-cyclodextrin derivatives that block the anthrax protective antigen pore. These compounds were at least 15-fold more potent than previously described beta-cyclodextrins in protecting against anthrax lethal toxin in a rat model. One of the drugs was shown to protect mice from bacterial infection.

FIG. 1.

Protection of mice from B. anthracis infection. Mice challenged with B. anthracis Sterne spores were treated on days 1 to 10 with compound 14b (2.5 mg/kg/day i.v.) alone, with ciprofloxacin (CIPRO) alone (50 mg/kg/day i.p.), or with both compound 14b and ciprofloxacin (by the same schedule used for each compound alone) and survival was monitored. The graph presents the results of a single representative experiment selected to show the lowest survival rates. The combination of ciprofloxacin with compound 14b was significantly (P = 0.02) more effective at protecting the mice than antibiotic treatment alone. In a second set of experiments, 90% of animals treated with compound 14b and ciprofloxacin survived.