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Web Date: February 8, 2007

Hunting For A Botulism Antidote

Chemical screening and animal trials suggest leads for treating the deadly disease
Department: Science & Technology
FIGHTING BACK
2,4-Dichlorocinnamic hydroxamic acid (top) and a still-unnamed compound (bottom) could serve as the basis for treatments for botulism.
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FIGHTING BACK
2,4-Dichlorocinnamic hydroxamic acid (top) and a still-unnamed compound (bottom) could serve as the basis for treatments for botulism.

Two compounds have been identified that could lead to potential drugs to combat botulin poisoning, which currently has few effective remedies (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0611213104).

The bacterial botulinum neurotoxin (BoNT) is a protein that can cause paralysis and death in microgram quantities. It's of particular interest because it "easily could be used in a bioterrorist attack," note Kim D. Janda of Scripps Research Institute and his colleagues.

The researchers screened a library of compounds for small molecules that disrupt the interaction between BoNT and the neural proteins it cleaves. Using kinetic analysis, cellular assays, and mouse trials, the team identified 2,4-dichlorocinnamic hydroxamic acid and a still-unnamed compound as leads for further optimization.

The researchers were frustrated because there was no correlation between the results of their cellular assays and animal studies. As such, they recommend development of in vitro cellular systems that more accurately predict the performance of antidotes in live animals.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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