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Updated: Jul 15, 2026
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Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
Amiodarone and bepridil inhibit anthrax toxin entry into host cells
Ana M Sanchez1, Diane Thomas, Eugene J Gillespie
1Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Antimicrobial Agents and Chemotherapy
|May 9, 2007
Summary
Researchers screened small molecules to find new ways to combat anthrax lethal toxin. Two heart medications, amiodarone and bepridil, showed potent anti-lethal toxin effects by blocking toxin entry into cells.
Area of Science:
- Microbiology
- Pharmacology
- Toxicology
Background:
- Bacillus anthracis lethal toxin is a key factor in anthrax virulence.
- Developing countermeasures against anthrax lethal toxin is crucial for public health.
- Existing treatments may have limitations, necessitating novel therapeutic strategies.
Purpose of the Study:
- To identify novel small molecules with anti-anthrax lethal toxin activity.
- To characterize the antitoxic properties of identified compounds.
- To investigate the mechanism of action for potent antitoxic compounds.
Main Methods:
- Screening of approximately 500 small molecules using a cell-based assay.
- Assessing the ability of compounds to protect RAW 264.7 macrophages from lethal toxin-mediated killing.
- Characterizing the two most potent compounds, amiodarone and bepridil.
- In vitro and in vivo testing of antitoxic efficacy and mechanism.
Main Results:
- Nineteen compounds demonstrated protective effects against anthrax lethal toxin.
- Amiodarone and bepridil were identified as the most potent antitoxic compounds.
- These drugs, used for cardiac conditions, protected macrophages at relevant concentrations.
- Antitoxic activity is attributed to blocking endosomal acidification and toxin entry.
- Amiodarone significantly enhanced survival in a lethal toxin-challenged rat model.
Conclusions:
- Amiodarone and bepridil possess significant anti-anthrax lethal toxin properties.
- Blocking endosomal acidification is a viable strategy to inhibit anthrax toxin.
- Existing cardiovascular drugs may offer potential as novel anthrax antitoxins.
- Further investigation into amiodarone and bepridil as anthrax therapeutics is warranted.
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