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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Research Article

Computational and Kinetic Studies of Acetylcholine Esterase Inhibition by Phenserine

Author(s): Shams Tabrez* and Ghazi A. Damanhouri

Volume 25, Issue 18, 2019

Page: [2108 - 2112] Pages: 5

DOI: 10.2174/1381612825666190618141015

Price: $65

Abstract

Background: The inhibition of cholinesterase enzymes is one of the promising strategies to manage several neurological disorders that include Alzheimer's disease (AD).

Material and Methods: In the current article, we estimated the potential inhibition of acetyl cholinesterase (AChE) by phenserine using slightly modified Ellman assay. To find out the binding interactions of phenserine with the catalytic site of AChE, a molecular docking study was also performed.

Results: Phenserine was found to inhibit Electrophorus electricus AChE in a dose-dependent manner with an IC50 value of 0.013 µM. The kinetic analyses indicate that phenserine inhibits AChE in a mixed type manner (competitive and uncompetitive) with Ki values of 0.39 μmole/l and 0.21 µmole/l, respectively. On the other hand, Km and Vmax values were found to be 0.17 µM and 0.39 µM, respectively. The molecular docking studies indicate efficient binding of phenserine through 6 hydrogen bonds, 4 pi-alkyl interactions, and 1 pi-pi interaction within the AChE catalytic pocket.

Conclusion: Results of our computational and kinetics studies indicated a mixed type inhibition by phenserine at AChE catalytic site.

Keywords: Acetylcholine esterase, inhibition, kinetics, molecular docking, phenserine, cholinesterase enzymes.

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