Background: Alzheimer's disease is caused by the destruction or loss of cholinergic cells
that produce or use ACh in the brain, thereby reducing the availability of enzyme to other cells. The
major treatment strategy for AD is to decrease the level of cholinesterase in the brain.
Objective: The aim of this study was to describe the effect of novel series of thiazole derivatives i.e.
arylidene aminothiazolylethanones (3a-h) as cholinesterase inhibitors (CEIs).
Method: A novel series of thiazole derivatives i.e. arylidene aminothiazolylethanones (3a-h) was
synthesized by treating 3-chloropentane-2,4-dione (1) with urea followed by reaction with suitably
substituted benzaldehydes. Structural confirmation of all the synthesized compounds was carried out
by spectroscopic techniques (FTIR, 1H and 13CNMR) and elemental analysis. Furthermore, these derivatives
were subjected to biological evaluation as potential inhibitors of cholinesterases i.e. acetylcholinesterase
(AChE) and butyrylcholinesterase (BChE).
Results: In all synthesized compounds except two compounds i.e. 3a and 3f, all compounds were
identified as selective inhibitors of AChE. Compound 3a exhibited potent inhibitory values against
AChE (IC50± SEM = 1.78±0.11 µM), exhibiting ≈7 times greater selectivity for AChE over BChE.
Kinetics studies were performed to find out the mechanism of inhibition against respective enzyme.
In addition, molecular docking studies of most potent inhibitors were also carried out to determine
the binding interactions with AChE and BChE, respectively.
Conclusion: In this study, novel thiazole derivatives i.e. arylidene aminothiazolylethanones were
successfully synthesized, characterized and further screened for threir potential as cholinesterase inhibitors.
All compounds were found as potent selective inhibitors of AChE except two compounds
which exhibited dual inhibitory activities but both of these compounds were highly selective toward
AChE as compared to BChE.