Background: Chalcones, originated from natural product, have been broadly studied
their biological activity against various proteins which at the molecular level, are responsible for
the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis
(cathepsins receptor), and diabetes (e.g. α-glucosidase).
Objective: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition
activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
Methods: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay
was conducted using Ellman Method.
Results: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively,
towards AChE and BChE inhibition. Molecular docking studies predicted that this activity
might be due to the interaction of the chalcones with important amino acid residues in the binding
site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440,
LEU286 and VAL288.
Conclusion: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either
fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic
chain is necessary at the meta-position of Ring B.