ache-in-3

AChE-IN-3 had inhibitory effect on AChE and stronger inhibitory effect on NO, with EC50 of 0.57 μM.

sEH/AChE-IN-3 (15) serves as a dual inhibitor targeting both soluble epoxide hydrolase (sEH) and acetylcholinesterase (AChE), demonstrating potent activity and the ability to cross the blood-brain barrier (BBB). It exhibits IC50 values of 0.4 nM for human sEH (hsEH), 1.94 nM for human AChE (hAChE), 615 nM for human butyrylcholinesterase (hBChE), 4.3 nM for mouse sEH (msEH), and 2.61 nM for mouse AChE (mAChE), indicating its efficacy across these enzymes.

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.

hAChE-IN-3 (compound 5c) serves as a potent inhibitor for AChE, BuChE, MAO-B, and BACE-1, with respective IC50 values of 0.44, 0.08, 5.15, and 0.38 μM, demonstrating its ability to cross the blood-brain barrier. This compound also exhibits antioxidant properties and metal chelation capabilities. Additionally, it targets peripheral anion sites, potentially modulating β-amyloid and ameliorating neurodegeneration linked to Alzheimer's disease, highlighting its research potential for this condition [1].

eeAChE-IN-3 (compound YS3g) is an orally bioavailable and potent inhibitor of EeAChE and IL-6, with IC50 values of 0.54 μM for EeAChE, 0.49 μM for RatAChE, 8.54 μM for RatBuChE, and 0.57 μM for IL-6. It can enhance learning and memory deficits in mice induced by STZ (streptozotocin) and shows potential for Alzheimer's disease (AD) research.

AChE-IN-39 (Compound 7c), with an IC50 value of 0.058 μM, is an acetylcholinesterase (AChE) inhibitor known for its DPPH scavenging activity and potential to ameliorate cognitive impairments in an aluminum chloride (AlCl3)-induced amnesia animal model, suggesting its usefulness in Alzheimer's disease research [1].

AChE-IN-31 (compound 1), a non-competitive acetylcholinesterase (AChE) inhibitor, exhibits potential for Alzheimer's disease research [1].

AChE-IN-30 is a small-molecule acetylcholinesterase inhibitor with an IC50 value of 4.4 μM that demonstrates neuroprotective activity by suppressing intracellular reactive oxygen species accumulation and inhibiting hydrogen peroxide–induced apoptosis, thereby serving as a research compound for Alzheimer’s disease models and oxidative stress–associated neuronal injury studies.

AChE-IN-34 (compound 5l) is a potent and selective AChE inhibitor with an IC50 of 3.98 µM, exhibiting negligible BChE inhibition. It demonstrates mixed-mode inhibition of AChE with a Ki of 0.044 µM using acetylthiocholine substrate concentrations ranging from 0.1-1 mM [1].

AChE-IN-35 (compound 5g) is an acetylcholinesterase inhibitor with an IC50 value of 5.88 μM [1].

AChE-IN-36 (compound A4) is an acetylcholinesterase inhibitor with an IC50 of 0.04 μM, affecting ROS levels and modulating NRF2 gene expression [1].

AChE-IN-37 (compound A2) is an acetylcholinesterase inhibitor with an IC50 of 0.23 µM, altering reactive oxygen species (ROS) levels and modulating the expression of nuclear factor erythroid 2-related factor 2 (NRF2) [1].

hBChE-IN-3 (compound 30) serves as both an activator of carbonic anhydrase (CA) and an inhibitor of cholinesterase (ChE), exhibiting IC50 values of 7.4 nM for AchE and 1.9 nM for BchE. This compound is utilized in the research of neurodegenerative and psychiatric disorders.

AChE/Aβ-IN-3 (Compound AM5) is a dual inhibitor of AChE and Amyloid-β aggregation, with IC₅₀ values of 1.29 and 4.93 μM, respectively. This compound exhibits antioxidant properties, reducing ROS and normalizing their levels. It is applicable in the study of neurological disorders such as Alzheimer's disease.

AChE-IN-92 (Compound L4R1-3) is a highly selective acetylcholinesterase (AChE) inhibitor with an IC50 of 4.6 nM. It effectively prevents the hydrolysis of acetylcholine, thereby increasing its levels in the synaptic cleft. AChE-IN-92 holds potential for research in Alzheimer's disease (AD).

Neuroprotective agent 15 (Compound 3e) acts as a neuroprotective agent that selectively inhibits butyrylcholinesterase (BChE), with IC50 values of 2.6 μM for BChE and 114.3 μM for acetylcholinesterase (AChE). It also functions as a cannabinoid CB2 receptor agonist. This compound reduces cell death, decreases LDH release and Caspase-3/7 activity, thereby inhibiting apoptosis. Additionally, it reduces superoxide radical formation, maintains cellular morphology, and lowers oxidative stress levels. Neuroprotective agent 15 is useful in studies of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

AChE-IN-105 (Compound C5) is a potent mixed-type AChE inhibitor with an IC50 value of 5.02 μM. It effectively scavenges ROS, reduces hydrogen peroxide-induced Caspase-3 activation, and inhibits the Nrf2-ARE pathway. In a Scopolamine-induced zebrafish cognitive impairment model, AChE-IN-105 prevents memory deficits and demonstrates strong antioxidant activity. It is applicable in Alzheimer's disease research.

Acotiamide is an orally active, selective, and reversible acetylcholinesterase (AChE) inhibitor with an IC50 of 1.79 μM. It is a gastroprokinetic agent that enhances gastric contractility and accelerates delayed gastric emptying, with potential for research in functional dyspepsia involving gastric motility dysfunction and intestinal inflammatory [1] [2] [3].

6,9-Dichloro-1,2,3,4-tetrahydroacridine is a synthetic intermediate in the synthesis of tacrine-based acetylcholinesterase (AChE) inhibitors.1It is also an intermediate in the synthesis of multifunctional tacrine hybrids that possess radical scavenging, amyloid-β aggregation inhibitory, and/or β-secretase 1 (BACE1) inhibitory activities in addition to their activity as AChE inhibitors.2,3 1.Recanatini, M., Cavalli, A., Belluti, F., et al.SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analoguesJ. Med. Chem.43(10)2007-2018(2000) 2.Digiacomo, M., Chen, Z., Wang, S., et al.Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of ADBioorg. Med. Chem. Lett.25(4)807-810(2015) 3.Li, S.Y., Jiang, N., Xie, S.S., et al.Design, synthesis and evaluation of novel tacrine-rhein hybrids as multifunctional agents for the treatment of Alzheimer's diseaseOrg. Biomol. Chem.12(5)801-814(2014)

Donecopride is a partial agonist of the serotonin (5-HT) receptor subtype 5-HT4E(Ki= 8.5 nM) and an inhibitor of acetylcholinesterase (AChE; IC50= 16 nM).1It is selective for AChE over butyrylcholinesterase (BChE; IC50= 3,530 nM) but does bind to 5-HT2Band sigma-2 (σ2) receptors (Ki= 1.6 nM for both) in a panel of 42 neurotransmitter receptors and transporters. Donecopride induces release of soluble amyloid precursor protein-α (sAPP-α) in COS-7 cells transiently expressing 5-HT4with an EC50value of 11.3 nM. Oral administration of donecopride (1 mg/kg) reduces brain soluble and insoluble amyloid-β (1-42) levels and increases the time spent exploring the novel object in the novel object recognition (NOR) test in the 5XFAD transgenic mouse model of Alzheimer's disease. Donecopride (3 mg/kg, p.o.) prevents a reduction in spontaneous alternation behavior induced by intracerebroventricular administration of soluble Aβ42 (sAβ42) in the Y-maze in mice.2 1.Lecoutey, C., Hedou, D., Freret, T., et al.Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatmentProc. Natl. Acad. Sci. USA111(36)E3825-E3830(2014) 2.Rochais, C., Lecoutey, C., Hamidouche, K., et al.Donecopride, a Swiss army knife with potential against Alzheimer's diseaseBr. J. Pharmacol.177(9)1988-2005(2020)

Rivastigmine carbamate impurity (3-Nitrophenyl ethyl(methyl)carbamate) is a byproduct found in Rivastigmine, a potent and orally active cholinesterase (ChE) inhibitor that effectively inhibits butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 0.037 μM and 4.15 μM, respectively.

1. Decursin (Decursinol angelate) is able to attenuate kainic acid-induced seizures and could have potential as an antiepileptic drug. 2. Decursin exhibits hepatoprotective effects , potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling. 3. Decursin has anti-cancer activity , mediated suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. 4. Decursin exhibits cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE 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.

α-Amylase-IN-3 is a multi-target inhibitor of α-amylase (IC50=18.04 μM) and cholinesterases (AChE/BChE). It exhibits antioxidant activity for diabetes and neurodegeneration research.