Background: Selective butyrylcholinesterase (BuChE)-inhibition, increases acetylcholine
(ACh) levels. In rodents, this inhibition is known to boost cognition. Also, this occurs without the
typical unwanted adverse effects of acetylcholinesterase-inhibitors or AChE-Is. The novel compound,
fluorobenzylcymserine (FBC), is derived from our effort to design a selective BuChE-inhibitor. Also,
we wanted to check whether butyrylcholinesterase-inhibitors (BuChE-Is) possessed an edge over
AChE-Is in Alzheimer's disease (AD) in terms of efficacy and/or tolerance.
Method: FBC was synthesized as reported earlier while enzymatic activity of BuChE was calculated
by Ellman-technique. Molecular docking was performed using Autodock4.2. We applied classical as
well as innovative analyses of enzyme-kinetics for exploring “FBC:human BuChE-interaction”. The
mode of inhibition and kinetic parameters were also determined.
Results: Docking results displayed two strong interacting sites for FBC. One of these binding sites was
previously identified as a deep narrow groove having polar aromatic residues while a second site was
identified during this study which displayed better interaction and was lined with aliphatic and sulphur
containing residues. At low concentrations of BuChE, the IC50 was found to be very low i.e. 4.79 and 6.10
nM for 12 and 36 µg, respectively, whereas it increased exponentially by increasing the units of BuChE.
Conclusion: These analyses indicate that FBC is an interesting AD drug candidate that could provide a
potent and partial mixed type of inhibition of human BuChE.