Acetylcholinesterase 2), similar to that of a chalcone. It

Background Information

            Acetylcholinesterase (AChE) is an
enzyme which plays an important role in regulating neural impulse
transmissions. Through the hydrolysis of the neurotransmitter acetylcholine,
neural impulse transmissions are terminated. In people with neurodegenerative
diseases such as Alzheimer’s, these neural impulse pathways are less active
than normal. To increase the activity of these pathways, inhibitors can be used
towards AChE in order to decrease the termination of the neural impulses. The
natural products of several plant species are known or suspected to be AChE
inhibitors, including caffeine and a variety of chalcone compounds.
Naturally-occurring chalcones, containing a 1,3-diaryl-2-propen-1-one backbone
(Figure 1), have been shown to inhibit AChE when containing certain
substituents, including hydroxyl groups which are responsible for hydrogen

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of Curcumin

            Curcumin is a natural product which
has a di-aryl structure containing ketone groups (Figure 2), similar to that of
a chalcone. It can be isolated from the spice turmeric, which originates in
India and Southeast Asia, and has been consumed for thousands of years due to
its wide range of medicinal properties. Turmeric, also referred to as Curcuma
longa, is part of the ginger family Zingiberaceae.  In addition to being a powerful antioxidant,
preventing biological damage due to free radicals, it has anti-inflammatory and
anti-aging properties. To measure its effect as an AChE inhibitor, readily
available turmeric will be purchased from Fortinos under the brand name Club
House for the price of $3.99 for 35g.



            The structure of the curcumin
backbone is very similar to the structure of the chalcone backbone. The
curcumin backbone is symmetrical about the centre carbon (Figure 3), and can be
visualized as two chalcone groups fused together. The major difference between
the two backbones is that the aryl group connected to the ketone carbon in the
chalcone is missing in curcumin. This could potentially lead to slight
differences in the properties of both molecules, even though both chalcones and
curcumin have a di-aryl structure.

            Each aryl group of curcumin has a
hydroxy and methoxy substituent attached to it. Methoxy groups are typically
responsible for electron donating, while hydroxy groups are primarily
responsible for hydrogen bonding. To cleave acetylcholine into its products,
acetate and choline, hydrogen bonding must occur at the catalytic triad of
serine, histidine, and glutamate in the esteratic subsite of AChE. This
hydrogen bonding is key in order to facilitate binding of inhibitor molecules
to AChE, and these intermolecular forces are what allow curcumin and certain chalcone
compounds to act as AChE inhibitors. Creation of strong hydrogen bonding by
inhibitors at the ligand binding site of AChE is what prevents the AChE enzyme
from functioning properly. The structure of caffeine (Figure 4) is quite
different from both curcumin and chalcone compounds, but due to the abundance
of electron-donating nitrogen and oxygen atoms, which are capable of hydrogen
bonding, caffeine also acts as an inhibitor of AChE.



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