Presentation Title

Synthesis of novel potential inhibitors of botulinum neurotoxins

Advisor Information

James Hagen

Location

Milo Bail Student Center Ballroom

Presentation Type

Poster

Start Date

8-3-2013 1:00 PM

End Date

8-3-2013 4:00 PM

Abstract

Botulinum neurotoxins are the most potent known neurotoxins, and are recognized by the Centers for Disease Control and Prevention as being extremely toxic to humans and their nervous system. The neurotoxin retards the neurotransmitter acetylcholine from entering the synaptic cleft; occurring throughout the whole human body but particularly within the human heart and lungs. Toxin-induced paralysis is the effect of toxin exposure which is often in the form of inhaled aerosols or food contamination; essentially leading to respiratory failure or cardiac arrest. The danger is that the neurotoxin (botulinum neurotoxin) produced by the bacterial species clostridium botulinum can be used as a biological warfare agent. Despite the fact that vaccines exist for these toxins they are available only to military laboratory workers. Furthermore the few vaccines that do exist have no effect on post-contaminated persons. With the ever growing population of our country and botulinum neurotoxin vaccines in short supply, the possibility of a terrorist attack using biological weapons is not something to be chanced leading to the need for new small molecule botulinum neurotoxin inhibitors in the United States bio-defense arsenal. In this study known botulinum neurotoxin inhibitor drug templates were utilized to synthesize potential inhibitors of botulinum neurotoxin that have not been previously considered. Once the novel inhibitors were developed their efficacy was determined thru biological testing by the United States Medical Research Institute of Infectious Diseases. Inhibitors that showed positive inhibition are being considered for further development in order to maximize the drug’s potency and activity.

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Mar 8th, 1:00 PM Mar 8th, 4:00 PM

Synthesis of novel potential inhibitors of botulinum neurotoxins

Milo Bail Student Center Ballroom

Botulinum neurotoxins are the most potent known neurotoxins, and are recognized by the Centers for Disease Control and Prevention as being extremely toxic to humans and their nervous system. The neurotoxin retards the neurotransmitter acetylcholine from entering the synaptic cleft; occurring throughout the whole human body but particularly within the human heart and lungs. Toxin-induced paralysis is the effect of toxin exposure which is often in the form of inhaled aerosols or food contamination; essentially leading to respiratory failure or cardiac arrest. The danger is that the neurotoxin (botulinum neurotoxin) produced by the bacterial species clostridium botulinum can be used as a biological warfare agent. Despite the fact that vaccines exist for these toxins they are available only to military laboratory workers. Furthermore the few vaccines that do exist have no effect on post-contaminated persons. With the ever growing population of our country and botulinum neurotoxin vaccines in short supply, the possibility of a terrorist attack using biological weapons is not something to be chanced leading to the need for new small molecule botulinum neurotoxin inhibitors in the United States bio-defense arsenal. In this study known botulinum neurotoxin inhibitor drug templates were utilized to synthesize potential inhibitors of botulinum neurotoxin that have not been previously considered. Once the novel inhibitors were developed their efficacy was determined thru biological testing by the United States Medical Research Institute of Infectious Diseases. Inhibitors that showed positive inhibition are being considered for further development in order to maximize the drug’s potency and activity.