Bridged bicyclic compounds: Comprehending a novel compound class as potential anti-seizure agents

Objective: In the present study, we describe a novel class of small-molecule synthetic compounds that ameliorate seizure-like behavior, using an electroshock assay to examine seizure duration in Caenorhabditis elegans. We also examine the hypothesis that these compounds, which we have called resveramorphs (RVMs), act by an irreversible binding mechanism. Methods: Our electroshock assay examines seizure duration in C. elegans and can be used as a drug-screening platform for the identification of novel anti-seizure agents. The use of C. elegans allows for a rapid and efficient method of drug screening that may take years in other higher-order model organisms. A novel wash method, paired with our electroshock assay, allows us to discern differences in biological activity when the C. elegans are incubated in different drug solutions, to establish whether these compounds can be “washed” off. Results: One of the RVMs (RVM-3), reported here for the first time, was found to be potent at picomolar concentrations. Insights also provided information on the potential mechanisms of action of this compound. Covalent binding is thought to provide a strong irreversible bond because of a change in structure between two of the novel RVMs described in this work. This was also discerned through the novel wash method paired with our electroshock assay. Significance: RVM-3 was evaluated using our assay and found to possess anti-seizure activity at picomolar concentrations. These insights also provide information on the potential mechanisms of action of these compounds, which may include covalent binding. This was also discerned through a novel wash method paired with our electroshock assay.