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/BChE-IN-3 (BMC-1) is an AChE and BChE dual inhibitor with IC 50 values of 6.08 μM for electric eel AChE (elAChE) and 0.383 μM for equine serum BChE (eqBChE), respectively [1].

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.

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 also exhibits an inhibitory effect on the aggregation of Aβ1-42. AChE/BuChE-IN-3 can be used to study Alzheimer's disease.

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

AChE/BChE/MAO-B-IN-3, an indan-1-one derivative, serves as a potent inhibitor of human monoamine oxidase B (MAO-B) with an IC50 of 0.0359 μM, demonstrating 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.

Dual AChE-MAO B-IN-3 (Compound C10) is a potent inhibitor of both AChE and MAO-B, exhibiting IC50 values of 0.58 μM and 0.41 μM, respectively. This dual-binding inhibitor 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.

hAChE-IN-6 (compound 51) is a brain-penetrant acetylcholinesterase (AChE) inhibitor exhibiting an IC50 of 0.16 μM. It also demonstrates inhibitory effects on 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), rendering it useful for Alzheimer's disease (AD) research [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.

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)

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].

AChE/BChE-IN-4 (BMC-3) is an AChE and BChE dual inhibitor that can cross the BBB. The IC 50 values of AChE/BChE-IN-4 for human AChE (hAChE) and human BChE (hBChE) are 792 nM and 2.2 nM, respectively[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].

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].

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.

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, which is recognized as a powerful and orally active inhibitor of cholinesterase (ChE). Specifically, Rivastigmine effectively inhibits both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), with IC50 values of 0.037 μM and 4.15 μM, respectively.