bche/ache-in-1

BChE/AChE-IN-1 (Compound 4m) is a potent dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC50 values of 0.7 μM and 0.2 μM, respectively. BChE/AChE-IN-1 holds potential for research into neurodegenerative diseases such as Alzheimer's disease (AD).

ChEs/MAOs-IN-1 (Compound 4i) is a dual inhibitor of cholinesterases (ChEs) and monoamine oxidases (MAOs). The IC50 values for ChEs/MAOs-IN-1 are 0.048 μM for AChE, 0.89 μM for BChE, 3.58 μM for MAO-A, and 0.095 μM for MAO-B. This compound can be utilized in studies related to neurodegenerative diseases.

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)

P11149, a derivative of Galanthamine, acts as a competitive, orally active, and selective AChE inhibitor with the ability to weakly penetrate the blood-brain barrier (BBB). It demonstrates selective inhibition, exhibiting an IC50 of 1.3 μM for rat BChE/AChE, and shows central cholinergic activity, behavioral efficacy, and safety. P11149 is utilized in Alzheimer's disease research[1].

1,3,5-Trihydroxy-4-prenylxanthone is a relatively potent inhibitor of phosphodiesterase type 5 (PDE5) with an IC50 of 3.0 μM; it exhibits in vitro inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 56.3plusmn;0.4 and 46.0plusmn;0.3 M, respectively. It also inhibits LPS-induced NF-κB and AP-1 activations by interfering with the posttranslational modification (phosphorylation and/or ubiquitinylation) of IRAK-1, disrupting TAK1-mediated activation of IKK and MAPKs signal transduction.

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.

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/BACE-1-IN-2 (Compound 4o) is an orally active AChE, BACE-1, and BChE inhibitor with IC50 values of 0.069, 0.097, and 0.127 μM against hAChE, hBACE-1, and hBChE, respectively. It exhibits remarkable antioxidant potential, considerable binding capability towards PAS-AChE, potential disassembly of Aβ aggregates, and neuroprotective activity against Aβ-induced stress with excellent brain permeation [1].

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].

AChE/BChE-IN-5 (BMC-16) is a dual inhibitor of AChE and BChE that can cross the BBB, with IC50 values of 266 nM for human AChE (hAChE) and 10.6 nM for human BChE (hBChE) [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/BChE/MAO-B-IN-1 is a reversible, non-time-dependent inhibitor of AChE, BChE, and MAO-B that crosses the blood-brain barrier, exhibiting inhibitory effects on hAChE, hBChE, and hMAO-B with IC50s of 7.31, 0.56, and 26.1 μM, respectively. [AChE/BChE/MAO-B-IN-1] had a neuroprotective effect and was not significantly cytotoxic.

BChE-IN-7 (compound 13) is a potent, selective, and reversible inhibitor of AChE and BChE, with an IC50 value of 0.06 μM for BChE. It can cross the blood-brain barrier and protect neuronal-like cells from toxic Aβ-species [1].

AChE/BChE/BACE-1-IN-1 (Compound 4k) is an orally active inhibitor that targets acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), with IC50 values of 0.058 μM, 0.082 μM, and 0.115 μM against hAChE, hBChE, and hBACE-1, respectively. It exhibits significant binding affinity with PAS-AChE, excellent blood-brain barrier permeability, potential disassembly of amyloid-beta (Aβ) aggregates, neuroprotective properties against Aβ-induced stress, and remarkable antioxidant capabilities [1].

AChE/BChE-IN-9 (Compound 7a) is a potent, orally active inhibitor of AChE and BChE, with IC50 values of 5.74 μM and 14.05 μM against hAChE and eqBChE, respectively. It also demonstrates effective antioxidant activity (IC50 = 57.35 μM), chelates iron, and modulates amyloid β 1-42 aggregation. Notably, AChE-IN-16 can cross the blood-brain barrier [1].

AChE/BChE-IN-1 is a potent dual inhibitor of acetylcholinesterase and butyrylcholinesterase with blood-brain barrier permeability, exhibiting IC50 values of 1.06 nM for hAChE and 7.3 nM for hBChE, and showing antioxidant effects. AChE/BChE-IN-1 can be used in 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/BChE/MAO-B-IN-4, an indan-1-one derivative, is a potent inhibitor of monoamine oxidase B (MAO-B) and acetylcholinesterase/butyrylcholinesterase (AChE/BChE). It strongly inhibits human MAO-B with an IC50 of 0.0393 μM and is highly effective against human AChE and BChE with IC50 values of 0.0458 μM and 0.075 μM, respectively. Additionally, this compound exhibits significant antioxidant properties and ability to prevent β-amyloid plaque aggregation, suggesting its potential in Alzheimer's disease (AD) research.

AChE/BChE-IN-11 (compound 1), a natural product derived from artichoke leaves, is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 70 μM and 71 μM, respectively. This compound is used in Alzheimer's disease (AD) research [1].

AChE/BChE-IN-15 (Compound 6d) is an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC50 values of 20 nM for AChE and 220 nM for BChE. It targets the catalytic anionic site (CAS) and the peripheral anionic site (PAS) within the enzymes' active centers. AChE/BChE-IN-15 is applicable in Alzheimer's disease research [1].

MAO-B-IN-24 (compound 11h) is a selective, reversible, competitive inhibitor of MAO-B with an IC50 value of 1.60 μM and an IC50 of 22.42 μM for MAO-A. At 10 μM concentration, it reduces AChE and BChE activities to 54.58% and 88.43%, respectively [1].

AChE/BChE-IN-13 (compound 5j) serves as a potent dual inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), exhibiting half-maximal inhibitory concentrations (IC50) of 20.89 μM for AChE and 17.37 μM for BChE, and is applicable in research related to Alzheimer's disease (AD) [1].

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/BChE-IN-14 (compound 13), a benzylisoquinoline alkaloid extracted from Fissistigma polyanthum roots, demonstrates inhibitory effects on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), coupled with antioxidant properties, and is pertinent to Alzheimer's disease research [1].