The Synthesis of Diarylpyridines as Inhibitors of Amyloid Beta Aggregation for Alzheimer’s Disease
Session Title
Poster Session 1
Faculty Mentor
Robin K. Lammi, Ph.D.| James M. Hanna Jr., Ph.D.
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Abstract
Amyloid-beta (A-beta) is a peptide which aggregates with other A-beta chains in the brain to form plaques which are correlated to the progression of Alzheimer’s Disease (AD). The amino acid phenylalanine plays a key role in aggregation through π-stacking interactions. Previous research in our group has shown that hydrogen bond donors on a biphenyl or terphenyl system can effectively inhibit aggregation, as well as those with a central phenyl linker region. To test how differences in the pi-stacking ability in an inhibitor affect aggregation, molecules with a central pyridine linker region, diphenylpyridinetetrol (DPPT) derivatives, were synthesized through Suzuki-Miyaura coupling followed by demethylation with hydrobromic acid (48% aq). Once the small molecules were synthesized, a Congo Red (CR) assay was performed on A-beta(40) to obtain data regarding the efficacy of inhibition. Products were synthesized in a wide range of yields, and preliminary CR assays showed possible inhibitory effects of some derivatives.
Previously Presented/Performed?
INBRE Science Symposium, Columbia, SC, February 2023 | Winthrop University Showcase of Undergraduate Research and Creative Endeavors, Rock Hill, SC, April 2023
Type of Presentation
Poster presentation
Grant Support?
Supported by an SC-INBRE grant from the National Institute for General Medical Sciences (P20GM103499).
Start Date
15-4-2023 12:00 PM
The Synthesis of Diarylpyridines as Inhibitors of Amyloid Beta Aggregation for Alzheimer’s Disease
Amyloid-beta (A-beta) is a peptide which aggregates with other A-beta chains in the brain to form plaques which are correlated to the progression of Alzheimer’s Disease (AD). The amino acid phenylalanine plays a key role in aggregation through π-stacking interactions. Previous research in our group has shown that hydrogen bond donors on a biphenyl or terphenyl system can effectively inhibit aggregation, as well as those with a central phenyl linker region. To test how differences in the pi-stacking ability in an inhibitor affect aggregation, molecules with a central pyridine linker region, diphenylpyridinetetrol (DPPT) derivatives, were synthesized through Suzuki-Miyaura coupling followed by demethylation with hydrobromic acid (48% aq). Once the small molecules were synthesized, a Congo Red (CR) assay was performed on A-beta(40) to obtain data regarding the efficacy of inhibition. Products were synthesized in a wide range of yields, and preliminary CR assays showed possible inhibitory effects of some derivatives.
