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Fluorescence properties and sequestration of peripheral anionic site specific ligands in bile acid hosts: Effect on acetylcholinesterase inhibition activity

Paper ID Volume ID Publish Year Pages File Format Full-Text
29896 44445 2016 10 PDF Available
Title
Fluorescence properties and sequestration of peripheral anionic site specific ligands in bile acid hosts: Effect on acetylcholinesterase inhibition activity
Abstract

•Fluorescence of AChE inhibitors is strongly modulated in bile acid (BA) medium.•Specific solvent effect plays an important role on their photophysics.•PI and EB affect AChE activity through mixed inhibition.•The IC50 potency of both the inhibitors decreases significantly in the presence of BA.•The modulated enzymatic parameters are consistent with sequestration ability of BA.

The increase in fluorescence intensity of model acetyl cholinesterase (AChE) inhibitors like propidium iodide (PI) and ethidium bromide (EB) is due to sequestration of the probes in primary micellar aggregates of bile acid (BA) host medium with moderate binding affinity of ca. 102–103 M− 1. Multiple regression analysis of solvent dependent fluorescence behavior of PI indicates the decrease in total nonradiative decay rate due to partial shielding of the probe from hydrogen bond donation ability of the aqueous medium in bile acid bound fraction. Both PI and EB affects AChE activity through mixed inhibition and consistent with one site binding model; however, PI (IC50 = 20 ± 1 μM) shows greater inhibition in comparison with EB (IC50 = 40 ± 3 μM) possibly due to stronger interaction with enzyme active site. The potency of AChE inhibition for both the compounds is drastically reduced in the presence of bile acid due to the formation of BA-inhibitor complex and subsequent reduction of active inhibitor fraction in the medium. Although the inhibition mechanism still remains the same, the course of catalytic reaction critically depends on equilibrium binding among several species present in the solution; particularly at low inhibitor concentration. All the kinetic parameters for enzyme inhibition reaction are nicely correlated with the association constant for BA-inhibitor complex formation.

Graphical abstractThe modulated kinetic parameters for AChE inhibition by peripheral anionic site (PAS) specific ligands like ethidium bromide (EB) or propidium iodide (PI) are strongly correlated with partitioning ability of the drug into the bile acid (BA) host medium.Figure optionsDownload full-size imageDownload as PowerPoint slide

Keywords
Fluorescence solvatochromism; AChE inhibitor; Bile acid; Time-resolved fluorescence; Association constant; Enzyme kinetics
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Fluorescence properties and sequestration of peripheral anionic site specific ligands in bile acid hosts: Effect on acetylcholinesterase inhibition activity
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 158, May 2016, Pages 192–201
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us