Presentation Title

Using Substituted Phenols to Readily Evaluate Features of Aromatic Compounds Important for Cholinesterase Inhibition

Start Date

November 2016

End Date

November 2016

Location

HUB 302-29

Type of Presentation

Poster

Abstract

Cholinesterases have gained attention for their association with Alzheimer’s disease (AD) and are divided into two major classes, acetylcholinesterases (AChE) and butyrylcholinesterases (BChE). While the biological function of AChE is well understood, the role of BChE remains unclear. Previous studies have shown that patients with AD tend to have a decrease in AChE activity, while BChE activity increases. These results have led to the development of BChE-specific inhibitors. Nevertheless, the exploration of potential cholinesterase inhibitors may provide more potent therapeutics for AD patients. Surveying the literature shows substituted aromatic groups are components of many cholinesterase inhibitors, but synthesizing and systematically evaluating the importance of aromatic substituents presents a significant challenge. To readily evaluate a series of aromatic compounds as inhibitors, the ability of substituted phenols to inhibit BChE and AChE was investigated. Relative inhibition was determined by performing kinetic assays using UV-Vis spectroscopy. While the 2-bromophenol inhibited the enzyme by two-fold, the 2,4-dibromophenol was the most effective inhibitor, showing 99.9% inhibition at 5mM. Further, compounds with larger substituents led to more potent inhibitors. At the ortho and para position, iodo substituents showed better inhibition than the fluoro, chloro, and bromo substituents. These studies can be used to help guide the inclusion of substituents in future developments of cholinesterase inhibitors.

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Using Substituted Phenols to Readily Evaluate Features of Aromatic Compounds Important for Cholinesterase Inhibition

HUB 302-29

Cholinesterases have gained attention for their association with Alzheimer’s disease (AD) and are divided into two major classes, acetylcholinesterases (AChE) and butyrylcholinesterases (BChE). While the biological function of AChE is well understood, the role of BChE remains unclear. Previous studies have shown that patients with AD tend to have a decrease in AChE activity, while BChE activity increases. These results have led to the development of BChE-specific inhibitors. Nevertheless, the exploration of potential cholinesterase inhibitors may provide more potent therapeutics for AD patients. Surveying the literature shows substituted aromatic groups are components of many cholinesterase inhibitors, but synthesizing and systematically evaluating the importance of aromatic substituents presents a significant challenge. To readily evaluate a series of aromatic compounds as inhibitors, the ability of substituted phenols to inhibit BChE and AChE was investigated. Relative inhibition was determined by performing kinetic assays using UV-Vis spectroscopy. While the 2-bromophenol inhibited the enzyme by two-fold, the 2,4-dibromophenol was the most effective inhibitor, showing 99.9% inhibition at 5mM. Further, compounds with larger substituents led to more potent inhibitors. At the ortho and para position, iodo substituents showed better inhibition than the fluoro, chloro, and bromo substituents. These studies can be used to help guide the inclusion of substituents in future developments of cholinesterase inhibitors.