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

AcetylcholinesteraseBackground Information            Acetylcholinesterase (AChE) is anenzyme which plays an important role in regulating neural impulsetransmissions. Through the hydrolysis of the neurotransmitter acetylcholine,neural impulse transmissions are terminated.

In people with neurodegenerativediseases such as Alzheimer’s, these neural impulse pathways are less activethan normal. To increase the activity of these pathways, inhibitors can be usedtowards AChE in order to decrease the termination of the neural impulses. Thenatural products of several plant species are known or suspected to be AChEinhibitors, 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 certainsubstituents, including hydroxyl groups which are responsible for hydrogenbonding.

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Sourceof Curcumin            Curcumin is a natural product whichhas a di-aryl structure containing ketone groups (Figure 2), similar to that ofa chalcone. It can be isolated from the spice turmeric, which originates inIndia and Southeast Asia, and has been consumed for thousands of years due toits wide range of medicinal properties. Turmeric, also referred to as Curcumalonga, 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 andanti-aging properties.

To measure its effect as an AChE inhibitor, readilyavailable turmeric will be purchased from Fortinos under the brand name ClubHouse for the price of $3.99 for 35g. CurcuminStructure            The structure of the curcuminbackbone is very similar to the structure of the chalcone backbone. Thecurcumin backbone is symmetrical about the centre carbon (Figure 3), and can bevisualized as two chalcone groups fused together. The major difference betweenthe two backbones is that the aryl group connected to the ketone carbon in thechalcone is missing in curcumin. This could potentially lead to slightdifferences in the properties of both molecules, even though both chalcones andcurcumin have a di-aryl structure.            Each aryl group of curcumin has ahydroxy and methoxy substituent attached to it. Methoxy groups are typicallyresponsible for electron donating, while hydroxy groups are primarilyresponsible for hydrogen bonding.

To cleave acetylcholine into its products,acetate and choline, hydrogen bonding must occur at the catalytic triad ofserine, histidine, and glutamate in the esteratic subsite of AChE. Thishydrogen bonding is key in order to facilitate binding of inhibitor moleculesto AChE, and these intermolecular forces are what allow curcumin and certain chalconecompounds to act as AChE inhibitors. Creation of strong hydrogen bonding byinhibitors at the ligand binding site of AChE is what prevents the AChE enzymefrom functioning properly. The structure of caffeine (Figure 4) is quitedifferent from both curcumin and chalcone compounds, but due to the abundanceof electron-donating nitrogen and oxygen atoms, which are capable of hydrogenbonding, caffeine also acts as an inhibitor of AChE.