acetylcholinesterase

Acetylcholinesterase (ACHE; EC 3.1.1.7) is a cholinergic enzyme mainly found in neuromuscular junctions and cholinergic type chemical synapses, and is often used in biochemical research. Acetylcholinesterase catalyzes the breakdown or hydrolysis of acetylcholine and some other choline esters that act as neurotransmitters into acetate and choline. Acetylcholinesterase's main role is to terminate neuronal transmission and signaling between synapses to prevent ACh spread and activation of nearby receptors [1] .

Polygalacic acid (Virgaureagenin G)(PA) significantly improves cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increases choline acetyltransferase (ChAT) activity, and elevates levels of acetylcholine (ACh) in the hippocampus and frontal cortex, PA also significantly ameliorates neuroinflammation and oxidative stress in mice; suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation. Polygalacic acid shows significant postingestive effects on Spodoptera littoralis larvae.

Methyl tridecanoate is a natural product.

Methacholine Chloride (Acetyl-β-methylcholine chloride) is a quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma.

Pyridostigmine(Regonol) is an acetylcholinesterase inhibitor that can treat myasthenia gravis by increasing acetylcholine at the postsynaptic motor endplate.

SEW06622 is a potent inhibitor of acetylcholinesterase (AChE) and beta-secretase-1 (BACE-1) and is a potential candidate for the treatment of Alzheimer's disease.

Y13g dihydrochloride is a potent inhibitor of interleukin 6 (IL-6) and acetylcholinesterase (AChE) (both targets of Alzheimer's disease (AD) progression are related). Y13g dihydrochloride reverses STZ-induced memory deficits and exhibits histopathology similar to normal animals.

N-(4-methoxyphenyl)prop-2-enamide (N-(4-Methoxyphenyl)acrylamide) is an acrylamide analog used as a molecular structural unit. It inhibits the enzyme acetylcholinesterase, increasing acetylcholine levels in the synaptic gap. It can also inhibit the breakdown of dopamine, leading to increased dopamine levels in the brain.

ACHE Inhibitor 12 inhibited acetylcholinesterase with an IC50 value of 0.38 µM.

ACHE-IN-38 is a potent Acetylcholinesterase inhibitor that can be used for the synthesis of compounds with anti-inflammatory, anti-tumor, and antibacterial activities.

Jatrorrhizine hydrochloride is a compound extracted from the roots of Berberis vulgaris with neuroprotective, antimicrobial, antiplasmodial, and antioxidant activities.Jatrorrhizine hydrochloride is an orally active and selective inhibitor of acetylcholinesterase (AChE), which inhibits norepinephrine (NE) uptake. It inhibits the uptake of norepinephrine (NE).

2-(4-methoxyphenyl)-2-oxoethyl 2-hydroxy-5-methylbenzoate is a pro-neurotropic drug used to enhance cognitive function by increasing the synthesis and release of acetylcholine in the brain as well as by inhibiting the breakdown of acetylcholine by acetylcholinesterase.

2-Thiomorpholinoethanol is a morpholine derivative that affects the nervous system by inhibiting the enzyme acetylcholinesterase (AChE) and increasing the amount of acetylcholine in the body.

β-NETA (α-NETA) is a stable, noncompetitive, slowly reversible choline acetyltransferase (ChAT) inhibitor with an IC50 of 9 μM and is a potent chemokine-like receptor-1 (CMKLR1) antagonist. β-NETA has anti-cancer activity[1][2]. β-NETA weakly inhibits cholinesterase (IC50=84 µM) and acetylcholinesterase (IC50=300 µM).

Scopoletin (Esculetin 6-methyl ether) is a plant growth factor derived from the root of Scopolia carniolica, inhibits of acetylcholinesterase (AChE).

Donepezil (Aricept) is a piperidine-based, potent, specific, and reversible inhibitor of acetylcholinesterase (AChE). It can be used for the treatment of mild to moderate dementia of the Alzheimer's type.

Pralidoxime Chloride (2-PAM chloride) is a useful agent in the treatment of organophosphate poisoning. Pralidoxime binds to organophosphate-inactivated acetylcholinesterase, used to combat poisoning by organophosphates or acetylcholinesterase inhibitors (nerve agents).

1. Linarin (Acacetin-7-O-rutinoside) (acacetin-7-O-β-d-rutinoside) shows selective dose dependent inhibitory effect on acetylcholinesterase. 2. Linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways. 3. Linarin prevents A beta-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3b and up-regulates Bcl-2. 4. The piperine significantly enhanced the oral absorption of Linarin in rats by inhibiting P-glycoprotein mediated cellular efflux during the intestinal absorption and likely simultaneously by inhibiting the metabolism of Linarin.

1. Kuwanon G (Moracenin B) as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers, it may potentially be utilized as an effective treatment for Type II diabetes mellitus. 2. Kuwanon G has anti-inflammatory activity, it can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response. 3. Kuwanon G is a potent inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B. 4. Kuwanon G shows acetylcholinesterase (AChE) and butyrylcholinesterase(BChE) inhibitory activities, it may be a promising candidate for preventive and therapeutic agents for Alzheimer's disease. 5. Kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. 6. Kuwanon G has antibacterial activity against oral pathogens. 7. Kuwanon G is a specific antagonist for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

Neoeriocitrin is a natural product isolated from Drynaria Rhizome, shows activity on proliferation and osteogenic differentiation in MC3T3-E1. Neoeriocitrin is a potent acetylcholinesterase (AChE) inhibitor.

1. Sinapine, an alkaloid from seeds of the cruciferous species, can be used as an effective natural compound for chemo-resistance. 2. Sinapine has antioxidant and radio-protective activities.

Ethoxysanguinarine (6-Ethoxydihydrosanguinarine) shows human blood acetylcholinesterase (HuAChE) and human plasma butyrylcholinesterase (HuBuChE) inhibitory activity, with IC50 values of 0.83 +/- 0.04 microM and 4.20 +/- 0.19 microM, respectively.

Galanthamine (Galantamine) is an acetylcholinesterase (AChE)inhibitor(IC50 : 500 nM), can reduce brain damage induced by hypoxia-ischemia.

Compound AChE-IN-42, also known as Compound 28, is an acetylcholinesterase (AChE) inhibitor with an inhibition constant (K i) of 0.44 μM [1].

Acetyllycoposerramine M, a lycopodine-type alkaloid extracted from Lycopodium japonicum, exhibits no inhibitory effect on acetylcholinesterase [1].

Pitofenone hydrochloride (Pitophenone hydrochloride), a spasmolytic compound, inhibits the acetylcholinesterase (AChE) activity from bovine erythrocytes and from electric eel with Kis of 36 and 45 μM, respectively.

Lycoclavanol exhibits acetylcholinesterase inhibition activity.

Macusine B is a dual inhibitor, has almost equal inhibitory activity on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

Mangostanol is an acetylcholinesterase (AChE) selective inhibitor.Mangostanol has anti-cancer activity, it shows significant activities against the CEM-SS cell line, with IC50 values of 9.6 microg/ml.

Nantenine is an acetylcholinesterase inhibitor, it functions as an effective antagonist against a wide range of MDMA-induced effects in mice. Nantenine has anticonvulsant effect, which seems attributable to its stimulation and the resultant decrease of Ca

Vincosamide is an alkaloid from Psychotria leiocarpa extract, inhibits the acetylcholinesterase (AChE) activity with anti-inflammatory activity. Vincosamide can effect relaxation of the supercoiled pBR322 plasmid DNA in the presence of Cu2+.

Pseudopalmatine exhibits antiplasmodial activity. It also shows anti-acetylcholinesterase (AChE) activity, with IC50 values of 1.8uM.

(-)-Asimilobine shows antioxidative, anti-acetylcholinesterase (AChE), anti-α±-glucosidase, anti-leishmanial and anti-fungal activities; it displays weak inhibition against Streptococcus mutans (ATCC 25175), with a minimum inhibition concentration (MIC) o

Pralidoxime Iodide, also named 2-PAM, is an antidote approved for reactivation of inhibited acetylcholinesterase (AChE) in organophosphate poisoning.

Coumarinic acid serves as a brain-penetrating inhibitor of AChE (acetylcholinesterase) and β-amyloid, with applications in anti-Alzheimer's drug research [1].

WAY-604603 is an active molecule, demonstrating inhibitory activity on the enzyme cholinesterase, more specifically on acetylcholinesterase (AChE), while concurrently exhibiting reversible effects. This activity was discerned utilizing standard laboratory procedures, and WAY-604603 has been identified to potentially enhance cognitive function by prolonging the activity of the neurotransmitter acetylcholine (ACh).

S-(-)-N-trans-Feruloyl normetanephrine, a natural product exhibiting weak anti-acetylcholinesterase activity, can be isolated from the aerial parts of Bassia indica Wight [1].

MAO-B-IN-26 (Compound IC9) serves as both a MAO-B and acetylcholinesterase inhibitor. It safeguards SH?SY5Y cells from Aβ-induced toxicity, including morphological alterations, reactive oxygen species (ROS) production, and membrane damage, while also preventing Aβ-triggered autophagy and apoptosis. As such, MAO-B-IN-26 holds potential as a neuroprotective agent in the context of Alzheimer’s disease [1].

Sinapine hydroxide, an alkaloid derived from the seeds of cruciferous plants, demonstrates a variety of beneficial properties including anti-inflammatory, anti-oxidant, anti-tumor, anti-angiogenic, and radio-protective effects. Additionally, it acts as an inhibitor of acetylcholinesterase (AChE), making it valuable for researching neurodegenerative conditions such as Alzheimer’s disease, ataxia, myasthenia gravis, and Parkinson’s disease[4].

Calyxamine B has inhibitory activity on acetylcholinesterase, the effect is comparable to the natural inhibitors.

1α,4β,7β-Eudesmanetriol and 1β,4β,7β-Eudesmanetriol can inhibit growth of Pseudomonas stutzeri with a MIC value of 117 uM, they also show remarkable activities against acetylcholinesterase enzyme with IC50 values ranging between 25 and 26 uM.

Methyl ganoderate A acetonide, a lanostane triterpene derived from the fruiting bodies of Ganoderma lucidum, serves as a potent acetylcholinesterase (AChE) inhibitor with an IC50 value of 18.35 μM. Its efficacy in inhibiting AChE suggests potential utility in Alzheimer’s disease (AD) research [1].

3-Hydroxycarbofuran, a principal metabolite of Carbofuran, acts as a reversible inhibitor of acetylcholinesterase (AChE) [1].

Fasciculin-I, a toxin isolated from mamba venom, exerts its toxicity primarily by inhibiting acetylcholinesterase (AChE). Additionally, it impedes the action of α-neurotoxins on nicotinic acetylcholine receptors and neutralizes cardiac toxins that interact with cell membranes [1].

Fenchlorphos (Dermafos) is a cholinesterase inhibitor, used as an insecticide.

K1833 is an inhibitor and reactivator of human acetylcholinesterase (hrAChE), exhibiting an inhibition concentration (IC50) of 58$. Additionally, K1833 demonstrates potent inhibition (IC50 = 0.57$) and minimal reactivation of human butyrylcholinesterase (hrBChE) [1].

hAChE-IN-5 (compound 49) is a dual inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBuChE), exhibiting inhibitory potency with IC50 values of 0.17 μM for both enzymes. Additionally, it demonstrates potent glycogen synthase kinase 3 beta (GSK3β) inhibition with an IC50 of 0.21 μM. The compound is an effective inhibitor of tau protein and Aβ1-42 peptide self-aggregation. It can virtually bind the peripheral anionic site (PAS), preventing amyloid-beta (Aβ)-induced neurotoxicity. hAChE-IN-5's ability to cross the blood-brain barrier (BBB) underpins its utility in the development of multitargeted anti-Alzheimer’s agents [1].

AChE-IN-45 (Compound 14) is an acetylcholinesterase (AChE) inhibitor exhibiting an IC50 value of 11.57±0.45 nM, and it demonstrates both antioxidant and neuroprotective activities [1].

Dehydroglaucine is an acetylcholinesterase inhibitor, it shows antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Candida albicans, and Aspergillus niger.

Methiocarb, a carbamate pesticide, is used as an insecticide, acaricide, bird repellent, and molluscicide. Methiocarb stimulates cholinergic by inhibiting reversibly acetylcholinesterase activity, making methiocarb a potent neurotoxin.