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.