Presentation Time: 4:00-4:20
Home University: N.C. A&T State University
Research Mentor: Jeffrey Aube, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy
Program: SOLAR & SURE
Research Title: Triazoles as Kappa Opioid Agonists
The United States opioid epidemic is caused, in part, due to the available opioid pain relievers having adverse effects like euphoria. One approach to addressing this is to develop an alternative opioid that does not induce side effects. Opioid receptor agonists may activate multiple pathways. The ability of an agonist to only activate one pathway is known as biased agonism. If a biased agonist is developed that only activates the pain-relieving pathway but not the side-effect pathway, one could potentially avoid the undesired side effects of known opioids. Our lab has been working on a class of compounds called triazoles that are biased agonists that function at the kappa opioid receptor through the G-protein pathway. Previous studies have identified triazoles as active, biased compounds, but with low metabolic stability. This work also suggests that sulfur is a site of metabolic instability. Therefore, we hypothesize that a bioisosteric replacement of sulfur with carbon will increase metabolic stability. In this project, we have successfully synthesized an active, carbon-linked triazole that will serve as the basis for future structure activity relationship campaigns.