Abstract
Characterization of the kinetic parameters of tolserine, a novel acetylcholinesterase (AChE) inhibitor of potential in the therapy of Alzheimer’s disease, to inhibit purified human erythrocyte AChE was undertaken for the first time. An
ic
50 value was estimated by three methods. Its mean value was found to be 8.13 nM, whereas the
ic
100 was observed to be 25.5 nM as calculated by single graphical method. The Michaelis–Menten constant (
K
m
) for the hydrolysis of the substrate acetylthiocholine iodide was found to be 0.08 mM. Dixon as well as Lineweaver–Burk plots and their secondary replots indicated that the nature of the inhibition was of the partial non-competitive type. The value of
K
i
was estimated as 4.69 nM by the primary and secondary replots of the Dixon as well as secondary replots of the Lineweaver–Burk plot. Four new kinetic constants were also investigated by polynomial regression analysis of the relationship between the apparent
K
i
(
K
Iapp) and substrate concentration, which may open new avenues for the kinetic study of the inhibition of several enzymes by a wide variety of inhibitors
in vitro. Tolserine proved to be a highly potent inhibitor of human AChE compared to its structural analogues physostigmine and phenserine.