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RESVERATROL-INSPIRED BRIDGED BICYCLIC COMPOUNDS: CHARACTERIZING A NOVEL ANTIEPILEPTIC DRUG CLASS
Title
RESVERATROL-INSPIRED BRIDGED BICYCLIC COMPOUNDS: CHARACTERIZING A NOVEL ANTIEPILEPTIC DRUG CLASS.
Creator
Stilley, Samantha E., Dawson-Scully, Kenneth, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
Epilepsy is a widely prevalent disease within the United States. It is estimated that about 1.2% of the total American population has active epilepsy, a condition of the brain that causes seizures. These seizures are marked by chemical alterations in neuronal firing that can cause abnormal behavior, sensations, muscle spasms, and loss of consciousness. Although the prevalence of seizures and epilepsy is high, effective treatments are limited and fail to provide effective treatment for nearly...
Show moreEpilepsy is a widely prevalent disease within the United States. It is estimated that about 1.2% of the total American population has active epilepsy, a condition of the brain that causes seizures. These seizures are marked by chemical alterations in neuronal firing that can cause abnormal behavior, sensations, muscle spasms, and loss of consciousness. Although the prevalence of seizures and epilepsy is high, effective treatments are limited and fail to provide effective treatment for nearly one-third of adult epileptic patients. Here, I conclude results of successful screening of novel compounds that can ameliorate seizures using an electroshock assay to examine seizure susceptibility and duration in C. elegans. The use of this assay provides an excellent platform for novel antiepileptic drug (AED) discovery efficiently. Literature shows Resveratrol, a natural product from plants, provides neuroprotective effects in various model organisms and therefore, is an excellent candidate for a molecule that has never been related to seizure. However, it is easily metabolized, being a flat and planar molecule. Our research group has collaboratively identified a novel bicyclic bridge molecule derived from the scaffolding of two resveratrol molecules we named Resveramorph (RVM). We also used the candidate approach to test a number of Resveramorph analogs on this assay to find the analog with highest efficacy. The various molecules characterized with their efficacy for seizure-like behavior after an electroshock have helped elucidate the mechanism of action and the RVMs physical target to give us greater insight into this potential family of AEDs.
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Date Issued
2022
PURL
http://purl.flvc.org/fau/fd/FA00014072
Subject Headings
Anticonvulsants, Epilepsy, Drug development, Caenorhabditis elegans
Format
Document (PDF)
USING ELECTROSHOCK TO PROBE MECHANISMS OF HERBICIDE NEUROTOXICITY AND NOVEL NEUROPROTECTIVE COMPOUNDS IN CAENORHABDITIS ELEGANS AND DROSOPHILA MELANOGASTER
Title
USING ELECTROSHOCK TO PROBE MECHANISMS OF HERBICIDE NEUROTOXICITY AND NOVEL NEUROPROTECTIVE COMPOUNDS IN CAENORHABDITIS ELEGANS AND DROSOPHILA MELANOGASTER.
Creator
Naraine, Akshay S., Dawson-Scully, Kenneth, Milton, Sarah, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
The communication in the nervous system is a pharmacological balance between excitatory and inhibitory signals, and seizure behavior is one of the most common manifestations of when an imbalance occurs. Environmental toxins can cause significant disruption of excitation-inhibition balance, but while some toxins, like nerve agents, have known targets and require novel antidotes, some have unknown neurobiological mechanisms and require exploration. Of particular concern, there is little...
Show moreThe communication in the nervous system is a pharmacological balance between excitatory and inhibitory signals, and seizure behavior is one of the most common manifestations of when an imbalance occurs. Environmental toxins can cause significant disruption of excitation-inhibition balance, but while some toxins, like nerve agents, have known targets and require novel antidotes, some have unknown neurobiological mechanisms and require exploration. Of particular concern, there is little knowledge on how herbicides may affect neurological signaling. Glyphosate, the world’s most popular herbicide, was found to be in 80% of people’s urine, and since it is so prevalent, it is critical to understand its impact on both excitatory and inhibitory signaling. We used an electroshock assay developed for C. elegans to uncover evidence that glyphosate, and the commercial formula Roundup, disrupted the excitation-inhibition balance by blocking GABA-A receptors. This presented a novel hypothesis of an inhibitory neurobiological target for glyphosate. As glutamate is the major excitatory neurotransmitter in the human central nervous system, an electrophysiology assay using Drosophila was used and found that Roundup, but not glyphosate, reduced synaptic viability. This result directs attention to the undisclosed adjuvant component which may have a significant effect on synaptic transmission, though the exact mechanism requires further investigation.
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Date Issued
2023
PURL
http://purl.flvc.org/fau/fd/FA00014151
Subject Headings
Seizures, Neurotoxins, Neuroprotective agents, Herbicides--Toxicology
Format
Document (PDF)