AChE

CV-6209 is a potent antagonist of the platelet-activating factor (PAF) receptor.

Timosaponin AIII (Timosaponin A3) induces autophagy in HeLa cells followed by apoptotic cell death (IC50: 10 μM). The Timosaponin AIII cellular response is mediated via inhibition of mTORC1 and induction of ER stress (IC50: 2.5 μM, BT474 cells; 6 μM, MDAMB231). The Timosaponin AIII pro-apoptotic response is selective for tumor cells over normal cells but autophagy is induced in both.

Physostigmine, a parasympathomimetic alkaloid, is a reversible cholinesterase inhibitor. It extracts from the Calabar bean.

Simpinicline (OC-02) (OC-02) is a highly selective nicotinic acetylcholine receptor (nAChR) agonist that activates the trigeminal parasympathetic pathway and can be used to treat dry eye.

Rovatirelin (S-0373) is a newly synthesized thyrotropin-releasing hormone (TRH) analog that ameliorates cytosine arabinoside-induced motor dysfunction in a rat model of spinal cerebellar degeneration via acetylcholine and dopamine neurotransmission.

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.

1. Huperzine-B is a efficient inhibitor of human brain AChE. 2. Huperzine-B can enhance ognitive and protect neuro, may be potentially new drug candidates for Alzheimer's disease therapy.

Nodakenin ((+)-Marmesinin) is a compound with anti-allergic and anti-inflammatory activities.

Tenuifolin has no inherent toxicity to either the transfected or wild type cells at the effective concentrations, it inhibits amyloid-β secretion in vitro.

Epiberberine chloride, a natural pro-berberine from Coptis chinensis Franch. is an AChE, BChE, and BACE1 inhibitor with IC50 values of 1.07, 6.03, and 8.55 μM, respectively.Epiberberine chloride has antioxidant effects and inhibits the effects of Ca9-22 and Fa2R. Epiberberine chloride has antioxidant effects, inhibits the motility of Ca9-22 and FaDu cell lines, and can be used to study hyperlipidemia, Alzheimer's disease and diabetes.

Jatrorrhizine (neprotin) is a protoberberine alkaloid isolated from Enantia chlorantha (Annonaceae) and other species. It was found to have antimicrobial and antifungal activity. It binds and noncompetitively inhibits monoamine oxidase (IC50 4 micromolar for MAO-A and 62 for MAO-B).

1. Epiberberine may be caused drug interactions based on CYP2D6 enzyme. 2. Epiberberine has anti-adipogenic effect is mediated by downregulation of the Raf MEK1 ERK1 2 and AMPKα Akt pathways during 3T3-L1 adipocyte differentiation. 3. Epiberberine, as the brightest FSA emitter among the alkaloids, can also serve as an efficient conformation probe for HTG DNA and discriminate the DNA G-quadruplex from the RNA counterpart.

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.

Jatrorrhizine chloride (Neprotine chloride) is a potent and orally active uptake-2 transporter inhibitor. It exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of the MAPK pathway in HT22 hippocampal neurons.

(+)-Pteryxin ((+)-Pteryxin) has muscle-relaxant props. (+)-Pteryxin shows hepatoprotective and nitric oxide prodn. inhibitory activity.

Loganin (Loganoside), an iridoid glucoside, has been reported to be an inhibitor of Cox-1 and also noted to suppress TNF-α formation. This compound also has displayed potent free-radical-scavenging activity and inhibitory effects on melanogenesis.

Donepezil HCl(Aricept) is a selective and effective AChE inhibitor for bAChE and hAChE (IC50: 8.12 11.6 nM).

Dehydroevodiamine (DHE), a natural compound isolated from Evodia rutaecarpa, can inhibit AChE. It has hypotensive and neuroprotective effects and modulates nitric oxide production.

Clozapine N-oxide dihydrochloride, a derivative of Clozapine and an agonist of human muscarinic design receptors (DREADDs), crosses the blood-brain barrier and activates DREADD receptors hM3Dq and hM4Di.

N-p-trans-Coumaroyltyramine is a natural product and an acetylcholinesterase (AChE) inhibitor with an IC50 of 122 μM. It also exhibits anti-trypanosomal activity with an IC50 of 13.3 μM for T. brucei rhodesiense.

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

1. Corynoline ((+)-Corynoline) is an acetylcholinesterase inhibitor.

Protriptyline Hydrochloride is the hydrochloride salt form of protriptyline, a tricyclic secondary amine with an antidepressant property. Protriptyline hydrochloride (Protriptyline HCl) blocks the re-uptake of norepinephrine and serotonin by nerve terminals, thereby increasing available norepinephrine and serotonin. In addition, this agent exhibits anticholinergic activity.

1. Acetylshikonin exhibits weak cytotoxicity against human umbilical vein endothelial cells (HUVECs) with IC5 of over 2 microM, exhibits the antiangiogenic and antitumorigenic effects by suppressing proliferation and angiogenic factors. 2. Acetylshikonin inhibits the generation of NADPH oxidase complex in the activation of respiratory burst of PMNs, but does not directly inhibit the activity of NADPH oxidase already generated. 3. Certain shikonin derivatives(such as Acetylshikonin) act as modulators of the Nur77-mediated apoptotic pathway and identify a new shikonin-based lead that targets Nur77 for apoptosis induction. 4. Acetylshikonin, shikonin, and alkannin have accelerative effect on the proliferation of granulation tissue in rats. 5. Acetylshikonin has inhibitory effect on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge. 6. Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress.

Pseudocoptisine chloride (Isocoptisine chloride) is isolated from Corydalis Tuber with anti-inflammatory and anti-amnestic properties. Pseudocoptisine chloride inhibits acetylcholinesterase (AChE) activity (IC50 = 12.8 μM).

sn-Glycero-3-phosphocholine (Choline glycerophosphate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have a potential for the treatment of Alzheimer's disease and dementia. sn-Glycero-3-phosphocholine rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of the acetylcholine neurotransmitter. It is a non-prescription drug in most countries due to its Generally Recognised As Safe (GRAS) status [1]. Studies have investigated its efficacy for cognitive disorders including stroke and Alzheimer's disease. An Italian multicentre clinical trial on 2, 044 patients suffering from recent stroke were supplied Glycerylphosphorylcholine in doses of 1, 000 mg day for 28 days and 400 mg three times per day for the five ensuing months. The trial confirmed the therapeutic role of alpha-GPC on the cognitive recovery of patients based on four measurement scales, three of which reached statistical significance [2].

Garcinol also inhibits histone acetyltransferases (HATs, IC50= 7 μM) and p300 CPB-associated factor (PCAF, IC50 = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity. Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.66 μM and 7.39 μM, respectively.

Chikusetsusaponin Ib (Chikusetsu saponin Ib) is an inhibitor of AChE and can be used in studies about anti-Alzheimer's diseases.

Drofenine hydrochloride (Hexahydroadiphenine hydrochloride) is an effective competitive inhibitor of BChE (Ki value: 3 uM).

Imperatorin (8-Isopentenyloxypsoralene) is a modulator of p38, ERK pathway. Imperatorin increases BMP-2 expression (mRNA) and increases bone density volume and mineralization in vivo.

Sinapine Thiocyanate, is a derivative of Sinapine (S486605), an alkaloidal amine found in black mustard seeds. It is the choline ester of Sinapic Acid (S486800). It is also a phenolic-chloine conjugates, acting as anti-oxidants and acetylcholinesterase inhibitors, that can be used for the treatment of Alzheimer's disease (AD).

Rhodiosin is a compound with antioxidant activity.

1. Palmatine (Burasaine) is an inhibitor of dopamine generation. 2. Palmatine could potentially be developed for the treatment of flavivirus infections. 3. Palmatine has been used in the treatment of jaundice, dysentery, hypertension, inflammation, and liver-related diseases.

Lycoramine is a natural product isolated from Lycoris radiate. Lycoramine is a potent acetylcholinesterase (AChE) inhibitor

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.

Rivastigmine (Exelon) is a Cholinesterase Inhibitor, used for therapy of Alzheimer disease.

Aldicarb sulfone is a cholinesterase inhibitor .

Arjunolic acid has antioxidant, anti-inflammatory, antinociceptive and anticholinesterasic (AChE and BuChE) activities, it may as promising targets for the development of innovative multi-functional medicines for Alzheimer desease treatment.

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.

Isoimperatorin is an anti-inflammatory agent, exhibits significant inhibitory effects on acetylcholinesterase (AChE).

Epi-galantamine, a diastereomer of galantamine, is an alkaloid extracted from the bulbs and flowers of the Caucasian snowdrop (Galanthus woronowii). It acts as an AChE inhibitor, featuring an EC50 of 45.7 μM.

Ursolic acid acetate (Acetylursolic acid) has cytotoxic activity, antimalarial activity, antitumor and anticancer activities. Acetylursolic acid has NO production inhibitory activities. Acetylursolic acid has inhibition against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.

Icopezil is a small molecule acetylcholinesterase in (AChE) inhibitor for the treatment of neurological disorders and can be used in the study of Alzheimer's disease.

Diazinon (Dimpylate) is a thiophosphoric acid ester, functioning as a nonsystemic organophosphate insecticide that effectively targets and controls a variety of pests including cockroaches, silverfish, ants, and fleas.

Galanthaminone ((-)-Narwedine) is a cholinesterase (AChE) inhibitor, is used for the treatment of mild to moderate Alzheimer's disease and various other memory impairments.

Hemicholinium 3 is a potent and selective choline uptake blocker.

Violanthin is a natural product isolated from the aerial parts of Piper bavinum and inhibits acetylcholinesterase (AChE) (IC50: 79.80 μM). It has potent antioxidant and antibacterial activities.

Dehydronuciferine, isolated from the leaves of Nelumbo nucifera Gaertn, exhibits acetylcholinesterase inhibition with an IC50 of 25 µg mL.