2-Hydroxyalbrassitriol (Compound 6) is an AChE inhibitor with an IC50 of 35.97 μM[1].
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[1]. 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[2].
Chlorpyrifos-oxon, an active metabolite of Chlorpyrifos, is a potent phosphorylating agent that potently inhibits AChE. Chlorpyrifos-oxon can induce cross-linking between subunits of tubulin and disrupt microtubule function[1][2][3][4].
BChE/HDAC6-IN-2 (compound 29a) is a dual inhibitor of BChE and HDAC6 with IC50s of 1.8 nM and 71.0 nM, respectively. BChE/HDAC6-IN-2 has prominently neuroprotective effects and reactive oxygen species (ROS) scavenging activity. BChE/HDAC6-IN-2 is also an effective chelator of metal ion (Fe2+ and Cu2+). BChE/HDAC6-IN-2 inhibits phosphorylation of tau, and exhibits moderate immunomodulatory effect.
Itopride-d6 (hydrochloride) is deuterium labeled Itopride (hydrochloride). Itopride hydrochloride (HSR803), a gastroprokinetic Benzamide (HY-Z0283) derivative, is an inhibitor of acetylcholinesterase (AChE) and dopamine D2 receptor[1][2].
Feralolide is a dihydroisocoumarin isolated from the methanolic extract of aloe vera resin. Feralolide is also a dual inhibitor of AChE and BuChE, with IC50s of 55 μg/mL and 52 μg/mL respectively. Feralolide has antioxidant activity and inhibits 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Feralolide could be used in research into cognitive disorders such as Alzheimer's disease, potentially restoring and enhancing memory[1].
Epiberberine is an alkaloid isolated from Coptis chinensis, acts as a potent AChE and BChE inhibitor, and a non-competitive BACE1 inhibitor, with IC50s of 1.07, 6.03 and 8.55 μM, respectively. Epiberberine has antioxidant activity, with peroxynitrite ONOO- scavenging effect (IC50, 16.83 μM), and may protect against Alzheimer disease[1]. Epiberberine inhibits the early stage of differentiation of 3T3-L1 preadipocytes, downregulates the Raf/MEK1/2/ERK1/2 and AMPKα/Akt pathways[2]. Epiberberine has the potential effect in the research of diabetic disease[3].
Ethopropazine (Isothazine) hydrochloride is a potent, selective BChE inhibitor and a poor AChE inhibitor. Ethopropazine hydrochloride is a phenothiazine compound with anticholinergic properties. Ethopropazine hydrochloride can be used for the research of Parkinson’s disease[1][2].
Donepezil(E 2020) is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM, respectively.Target: AChEDonepezil is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM , respectively [1]. Donepezil inhibits the carbachol-stimulated increase in intracellular Ca2+ concentration in human SHSY5Y neuroblastoma cells in a concentration dependent manner, indicating that Donepezil have muscarinic antagonist activity. Intraperitoneal administration of Donepezil in rats produces a dose dependent increase in salivation and tremor, which are overt cholinergic behavioural signs, with an ED50 of 6 μmol/kg. Donepezil is found to be somewhat less potent with a ED50 of 50 μmol/kg following oral administration [2]. A recent study shows that Donepezil can protect human umbilical vein endothelial cells (HUVECs) against H2O2-induced cell injury. This may be useful as a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases [3].
PCS1055 dihydrochloride is a potent, selective and competitive muscarinic M4 receptor antagonist with an IC50 of 18.1 nM and a Kd of 5.72 nM. PCS1055 dihydrochloride inhibits radioligand [3H]-NMS binding to the M4 receptor with a Ki of 6.5 nM. PCS1055 dihydrochloride exhibits >100-fold selectivity over M1-, M3-, and M5-receptors and 30-fold selectivity at the M2 receptor. PCS1055 dihydrochloride is also a potent AChE inhibitor with IC50 s of 22 nM and 120 nM for electric eel and human AChE, respectively[1][2].
AChE/BChE-IN-2 (Compound 13b) is a potent inhibitor of AChE/BChE (AChE IC50 = 0.96 ± 0.14 µM, BChE IC50 = 1.23 ± 0.23 µM). AChE/BChE-IN-2 has the potential for the research of AD diseases[1].
Itopride hydrochloride is an AChE inhibitor (acetylcholinesterase) and D2DR inhibitor.Target: AChEItopride is a gastroprokinetic benzamide derivative. The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. the IC50s of itopride against ChE activities were found to be about 0.5 microM. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively [1].
Tenuifolin is a triterpene isolated from Polygala tenuifolia Willd, has neuroprotective effects. Tenuifolin reduces Aβ secretion by inhibiting β-secretase. Tenuifolin improves learning and memory in aged mice by decreasing AChE activity and has the potential for Alzheimer’s disease (AD) treatment[1].
Geissoschizoline ((+)-Geissoschizoline) is a potent inhibitor of human AChE/BChE, with IC50s of 20.40 µM and 10.21 µM, respectively. Geissoschizoline emerges as a possible multi-target prototype that can be very useful in studies of preventing neurodegeneration and restoring neurotransmission. Geissoschizoline aiso is a potent anti-inflammatory agent[1].
Violanthin is isolated from the aerial parts of Piper bavinum, has potent antioxidant and antibacterial activities. Violanthin inhibits acetylcholinesterase (AChE) with an IC50 value of 79.80 μM[1].
AChE/BChE-IN-11 (compound 1) is a potent is a dual AChE and BChE inhibitor with IC50 values of 70 and 71 μM for AChE and BChE, respectively. AChE/BChE-IN-11 is a natural product that could be isolated from the leaf of artichoke . AChE/BChE-IN-11 can be used in research of Alzheimer’s disease (AD) research[1].
AChE-IN-19 (compound A15) is a highly potent AChE inhibitor with an IC50 value of 0.56 μM, also inhibits Aβ aggregation. AChE-IN-19 has potent neuroprotective activities and nearly no toxicity on SH-SY5Y cells. AChE-IN-19 can be used for researching Alzheimer's disease[1].
AChE-IN-17 (compound 1) is a potent AChE inhibitor with an IC50 value of 28.98 μM. AChE-IN-17 can significantly prevent H2O2-induced PC12 cell death, exhibiting excellent neuroprotective effect. AChE-IN-17 can be used for researching neurodegenerative diseases (NDs)[1].
Neostigmine methyl sulfate is a reversible inhibitor of acetylcholinesterase, can not cross the blood-brain barrier.
Pridinol mesylate is an orally active and potent central anticholinergic agent, and acts as muscle relaxant[1].
GSK1034702 is a M1 mAChR allosteric agonist. GSK1034702 shows procognitive effects in rodents. GSK1034702 modulates hippocampal function to improve memory encoding in nicotine abstinence model of cognitive dysfunction[1].
Donepezil-d5 is deuterium labeled Donepezil. Donepezil (E2020 free base) is a specific and potent AChE inhibitor with IC50s of 8.12 nM and 11.6 nM for bovine AChE and human AChE, respectively[1].
Acephate is an anticholinesterase insecticide that produces cholinotoxicity. Acephate displays weak inhibition of rat AChE but potently inhibits cockroach AChE.
AChE/BuChE-IN-4(compound 4a) is aorally activeandbrain-penetrantmultitarget-directedAChE/BuChEinhibitor againstAChEandBuChE, with theIC50of 2.08 and 7.41 μM[1].
T 82 is a potent 5-HT3 antagonist and acetylcholinesterase (AChE) inhibitor, used for treatment of Alzheimer's Disease.
4-Methylbenzylidene camphor(4-MBC; Enzacamene)is an organic camphor derivative that is used in the cosmetic industry for its ability to protect the skin against UV, specifically UV B radiation.
Acacetin-7-O-β-D-galactopyranoside is a flavonoid that can be isolated from flower heads of Chrysanthemum morifolium. Acacetin-7-O-β-D-galactopyranoside inhibits AChE activity and can be used for research of Alzheimer’s disease[1].
A potent, selective choline kinase α (ChoKα) inhibitor with IC50 of 0.12 uM, >400-fold selectivity over ChoKβ; demonstrates in vitro antiproliferative activity against HT29 cells with IC50 of 2.08 uM.
Ladostigil (TV-3326) hydrochloride is an orally active dual inhibitor of cholinesterase and brain-selective monoamine oxidase (MAO), with IC50s of 37.1 and 31.8 μM for MAO-B and AChE, respectively. Ladostigil hydrochloride exhibits neuroprotective, antioxidant and anti-inflammatory activities. Ladostigil can be used for the research of depression and Alzheimer's disease[1][2].
L-Alpha glycerylphosphorylcholine (alpha-GPC, choline alfoscerate) is a natural choline compound found in the brain and in milk. It is also a parasympathomimetic acetylcholine precursor which may have potential for the treatment of Alzheimer's disease and dementia.IC50 value:Target: Anti-ADAlpha-GPC 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 alpha-GPC 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].