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

AChE BChE-IN-3 (BMC-1) is a dual inhibitor of AChE and BChE, with IC50 values of 6.08 μM for electric eel AChE (elAChE) and 0.383 μM for equine serum BChE (eqBChE), respectively [1].

AChE BChE-IN-3 (BMC-1) hydrochloride is a dual inhibitor of AChE and BChE, with IC50 values of 0.383 μM against equine serum BChE (eqBChE) and 6.08 μM against electric eel AChE (elAChE) [1].

AChE BuChE-IN-3 is a potent inhibitor of AChE (IC50: 0.65 μM) and BuChE (IC50: 5.77 μM) that crosses the blood-brain barrier and inhibits the aggregation of Aβ1-42, suitable for Alzheimer's disease research.

AChE BChE MAO-B-IN-3, an indan-1-one derivative, is a potent inhibitor of human monoamine oxidase B (MAO-B) with an IC50 of 0.0359 μM and also demonstrates significant inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 0.0473 μM and 0.0782 μM, respectively. Exhibiting notable antioxidant activity, AChE BChE MAO-B-IN-3 holds considerable promise for Alzheimer's disease (AD) research.

AChE MAO-B-IN-3 is a dual inhibitor targeting both acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B), exhibiting inhibitory concentrations (IC50s) of 0.0257 μM and 0.0456 μM against human AChE and MAO-B, respectively. This compound holds potential for Alzheimer's disease research.

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.

Dual AChE-MAO B-IN-3 (Compound C10) is a potent inhibitor of both AChE and MAO-B, with IC50 values of 0.58 μM and 0.41 μM, respectively. It targets the catalytic anionic site and peripheral anionic site of AChE, making it relevant for Alzheimer's disease (AD) research [1].

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.

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.

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.

AChE BChE-IN-4 (BMC-3) is an AChE and BChE dual inhibitor that can cross the BBB, with IC50 values for human AChE (hAChE) and human BChE (hBChE) of 792 nM and 2.2 nM, respectively[1].

BChE-IN-3 is a selective, selective, time-dependent, pseudo-irreversible inhibitor of BChE butyrylcholinesterase (IC50: 56.9 nM).BChE-IN-3 exhibits borderline reversible (time-independent) inhibition of AChE acetylcholinesterase.

AChE-IN-29, a 3-OH pyrrolidine derivative, acts as a cholinesterase (ChE) inhibitor with potent activity against human acetylcholinesterase (hAChE), electric eel acetylcholinesterase (eeAChE), and equine butyrylcholinesterase (eqBChE), exhibiting IC50 values of 0.25 μM, 0.23 μM, and 0.72 μM, respectively. It is utilized in Alzheimer's disease research [1].

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].

Feralolide, a dihydroisocoumarin from the methanolic extract of aloe vera resin, functions as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), with IC50 values of 55 μg mL and 52 μg mL, respectively. It exhibits antioxidant properties, effectively inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Research suggests feralolide's potential in studying cognitive disorders, including Alzheimer's disease, for its memory restoration and enhancement capabilities [1].

hAChE-IN-6 (compound 51) is a brain-penetrant acetylcholinesterase (AChE) inhibitor with an IC50 of 0.16 μM. It also inhibits human butyrylcholinesterase (hBuChE) and glycogen synthase kinase 3 beta (GSK3β), with IC50 values of 0.69 μM and 0.26 μM, respectively. Additionally, hAChE-IN-6 impedes the self-aggregation of tau protein and amyloid-beta 1-42 (Aβ1-42), making it useful for Alzheimer's disease (AD) research [1].