Cholinesterase (ChE) Inhibitor

Gypsogenin is a selective mixed-type BChE inhibitor (K_i=19.99 μM) that also exhibits significant cytotoxicity against various human cancer cell lines. Gypsogenin inhibits tumor growth by inducing cell cycle arrest and triggering apoptosis. Gypsogenin displays antibacterial activity against bacteria such as Bacillus subtilis and Bacillus thuringiensis, and often serves as a key parent nucleus for the synthesis of anticancer compounds. Gypsogenin is widely used in research on Alzheimer's disease and various cancers including colon cancer, melanoma, and leukemia.

Polygalacic acid, is a triterpene, isolated from the root of Polygala tenuifolia Willd. Polygalacic acid inhibits MMP expression. Polygalacic acid may have a therapeutic effect in Osteoarthritis (OA) treatment . Polygalacic acid exerts a significant neuroprotective effect on cognitive impairment, PA improves cholinergic system reactivity by inhibiting acetylcholinesterase (AChE) activity, increasing choline acetyltransferase (ChAT) activity, and elevating levels of acetylcholine (Ach) in the hippocampus and frontal cortex.

Phenoxyacetone is a competitive acetylcholinesterase (AChE) inhibitor.

Dehydroevodiamine is a blood-brain barrier-permeable, orally effective AChE and BACE1 inhibitor (IC₅₀ = 40.96 μM). Dehydroevodiamine is isolated and extracted from Evodia rutaecarpa. Dehydroevodiamine attenuates neurotoxicity through multiple targets by inhibiting BACE1 to block Aβ production, inhibiting AChE activity, scavenging ROS, and suppressing calcium influx. Dehydroevodiamine can be used for research on Alzheimer's disease, cerebral ischemia, vascular dementia, and other cognitive disorder-related diseases.

2,2'-Dihydroxy-1,1'-binaphthyl is an acetylcholinesterase (AChE) inhibitor with an IC₅₀ value of 21.9 μM against human AChE. 2,2'-Dihydroxy-1,1'-binaphthyl exhibits cytotoxicity against Artemia nauplii.

9-Acridinecarboxylic acid is a precursor of a cholinesterase inhibitor, and its derivatives have nanomolar inhibitory potency against AChE and BChE.

Tacrine hydrochloride (hydrate) is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC₅₀s of 31 nM and 25.6 nM, respectively.

Ipidacrine is orally active and brain-penetrant AChE and BuChE inhibitors with IC₅₀ values of 1 μM and 1.9 μM, respectively, which is also a partial agonist of M2-cholinergic receptors and a reversible cholinesterase inhibitor. Ipidacrine has a stimulating effect on neuromuscular transmission and excitation along the nerve fibres with a moderately anti-pain effect. Ipidacrine is an aminopyridines and is structurally similar to Tacrine (HY-111338). Ipidacrine is effective in various amnesia models, improves erectile function and inhibits K⁺ and Na⁺-channels in the neuronal membrane in diabetic rats. Ipidacrine is promising for research of Alzheimer’s disease, ischaemic stroke, idiopathic neuropathy of the facial nerve, diabetes mellitus-induced erectile dysfunction and other deficits in central or peripheral cholinergic deseases.

Theasaponin E1 is an orally effective tea saponin. Theasaponin E1 inhibits the proliferation of cancer cells by activating apoptosis. Theasaponin E1 inhibits angiogenesis in ovarian cancer cells and HUVECs by reducing the expression of VEGF. Theasaponin E1 upregulates the phosphorylation level of ATM protein and the expression level of PTEN protein in cancer cells, decreases the phosphorylation levels of Akt, mTOR, p70S6K and 4E-BP1 proteins, downregulates the expression of HIF-1α and NF-κB, and reduces the protein expression of Notch ligands Dll4 and Jagged1. Theasaponin E1 exerts neuroprotective effects by inhibiting the activity of acetylcholinesterase, activating α-secretase and neprilysin, reducing the concentration of Aβ, and inhibiting the activities of β-secretase and γ-secretase. Theasaponin E1 exhibits toxic effects on cancer cells and quinone reductase-inducing activity, and inhibits tumor growth in vivo. Theasaponin E1 induces ferroptosis in Pomacea canaliculata by synergistically disrupting cholesterol homeostasis and sphingolipid metabolism. Theasaponin E1 possesses anti-biofilm activity against Candida albicans. Theasaponin E1 can be used in the research of ovarian cancer, obesity, Alzheimer's disease and fungal infections.

4,4'-Dimethoxybenzil is a human intestinal carboxyl esterase (hiCE) inhibitor with K_i of 70 nM.

Methylene Violet 3RAX is a phenazine dye to stain the mitochondria of cells. Methylene Violet 3RAX can change the molecular structure of DNA, undermine the module of DNA, and induce the generation of the reactive singlet oxygen. Methylene Violet 3RAX shows inhibition for human erythrocyte AChE and human plasma BChE with an K_is of 1.58, 0.51 μM, respectively. Methylene Violet 3RAX has the potential for the research of potential photosensitizers for mitochondrial targeting action in PDT (photodynamic therapy).

Chlorpyrifos-d₁₀ is the deuterium labeled Chlorpyrifos. Chlorpyrifos is an organophosphate insecticide that is classified as a phosphorothionate. The oxon metabolite of Chlorpyrifos is an inhibitor of acetylcholinesterase (AChE), affecting neurological function in insects, humans, and other animals. The Chlorpyrifos oxon (CPO) metabolite is hydrolyzed by the plasma enzyme paraoxonase 1 (PON1), and susceptibility to neurotoxicity associated with CPO exposure is mitigated by PON1 overexpression.

Isoprocarb is carbamate insecticide that widely used to control rice paddy lice and leafhopper. Isoprocarb is also an AChE inhibitor.

Vitisin A ((+)-Vitisin A) is an orally active natural product with multiple pharmacological activities including anti-inflammatory, anti-tumor, anti-oxidant, anti-pathogenic microorganism, hypoglycemic and lipid-regulating, anti-osteoporotic, neuroprotective and cardiovascular protective effects. Vitisin A exhibits inhibitory effects on human AChE and MAO-B with IC₅₀ values of 1.29 µM and 4.94 µM, respectively. Vitisin A inhibits the ERK, MAPK, NF-κB, STAT1, HMGCR and TRAF6 pathways, downregulates the related phosphorylation and protein expression, while activates the Nrf2/HO-1 pathway and upregulates p21 expression. Vitisin A induces tumor cell apoptosis and cell cycle arrest, inhibits adipogenesis and lipid accumulation, while alleviates oxidative stress, suppresses inflammatory responses, blocks hepatic fibrosis, Cuproptosis and cholesterol synthesis, and increases the expression levels of central BDNF and TrkB. Vitisin A can be used in the research of tumors, infectious diseases, metabolic diseases, bone and joint diseases, liver diseases, skin injuries, as well as neurodegenerative and cognitive dysfunction-related diseases.

Picfeltarraenin IB, a triterpenoid obtained from Picriafel-terrae Lour (P.fel-terrae), is an acetylcholinesterase (AChE) inhibitor. Picfeltarraenin IB can be used for the treatment of herpes infections, cancer and inflammation.

Ladostigil (TV-3326) hemitartrate is an orally active dual inhibitor of cholinesterase and brain-selective monoamine oxidase (MAO) that can cross the blood-brain barrier, with IC₅₀s of 37.1 and 31.8 μM for MAO-B and AChE, respectively. Ladostigil hemitartrate exhibits neuroprotective, antioxidant and anti-inflammatory activities. Ladostigil hemitartrate can be used for the research of depression and Alzheimer's disease. Ladostigil (hemitartrate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

Pseudocoptisine (Isocoptisine) chloride is a quaternary alkaloid with benzylisoquinoline skeleton, was isolated from Corydalis Tuber. Pseudocoptisine chloride inhibits acetylcholinesterase (AChE) activity with an IC₅₀ of 12.8 μM. Anti-inflammatory and anti-amnestic effects.

Fenchlorphos, an organophosphate, is an insecticide. Fenchlorphos is an inhibitor of the enzyme acetylcholinesterase (AChE). Fenchlorphos is able to cause mitochondrial dysfunction.

Amprolium hydrochloride is a thiamine transporter inhibitor and antiparasitic agent with oral activity and blood-brain barrier penetration. Amprolium hydrochloride blocks thiamine transport at the blood-brain barrier and intestine, and competitively inhibits thiamine pyrophosphokinase, inducing thiamine pyrophosphate deficiency and impairing carbohydrate synthesis. Amprolium hydrochloride induces oxidative stress, alters antioxidant enzyme activity, and inhibits acetylcholinesterase (AchE) activity. Amprolium hydrochloride disrupts reproductive organs and gametogenesis, and causes histopathological and ultrastructural damage to multiple organs. Amprolium hydrochloride induces thiamine deficiency, reduces body weight gain in mice, and causes psychomotor behavioral changes and nephropathy. Amprolium hydrochloride exhibits molluscicidal activity against the terrestrial snail Eobania vermiculata, and reduces the shedding of Eimeria meleagrimitis oocysts in feces and litter. Amprolium hydrochloride can be used for research on thiamine deficiency and coccidiosis.