Background: Cholinesterase family consists of two sister enzymes; acetylcholinesterase
(AChE) and butyrylcholinesterase (BChE) which hydrolyze acetylcholine. Since deficit of acetylcholine
has been evidenced in patients of Alzheimer's disease (AD), cholinesterase inhibitors are currently
the most prescribed drugs for the treatment of AD.
Objective: our aim in this article was to investigate the inhibitory potential of five known compounds
(2-6) with spiro skeleton against AChE and BChE using ELISA microplate assays. In addition to their
ChE inhibitory effect, their physico-chemical properties were also calculated. Moreover, the present
work aims at investigating the charge/geometrical effect of a hypothetical pharmacophore or bidentate
site in a bioactive group, on the inhibition efficiency of spiro compounds 2-6 by using Petra/Osiris/
molinspiration (POM) and X-ray analyses.
Method: In the present study, five compounds (2-6) with spiro skeleton have been synthesized and
tested in vitro for their inhibitory potential against AChE and BChE using ELISA microtiter plate assays
at 25 µg/mL.
Results: Results revealed that three of the spiro compounds tested exert more than 50% inhibition
against one of cholinesterases. Compound 5 displayed 68.73 ± 4.73% of inhibition toward AChE,
whereas compound 6 showed 56.17 ± 0.83% of inhibition toward BChE; these two previously synthesized
compounds have been the most active hits.
Conclusions: Our data obtained from screening of compounds 2-6 against the two cholinesterases indicate
that three of these show good potential to selectively inhibit AChE or BChE. Spiro compounds
2, 5, and 6 exhibited the most potent activity of the series against AChE or BChE with inhibition values
in the range 55-70%.