BChE Inhibitor

hAChE-IN-9 (compound 7i) is a selective inhibitor of human acetylcholinesterase (hAChE) with IC₅₀ of 0.05 μM and 2.85 μM for AChE and BChE, respectively. hAChE-IN-9 modulates toxic Aβ oligomer forms into non-toxic ones and has antioxidant and neuroprotective effects against Aβ-induced toxicity. hAChE-IN-9 can be used for the study of Alzheimer's disease.

ChE/GSK-3β-IN-1 (compound 18o) is a potent dual ChE/GSK-3β inhibitor. ChE/GSK-3β-IN-1 exhibits dual inhibition of AChE (IC₅₀ = 1.7 μM), butyrylcholinesterase (BChE) (IC₅₀ = 5.3 μM), and GSK-3β (IC₅₀ = 5.7 μM). ChE/GSK-3β-IN-1 inhibits Aβ1-42 self-aggregation. ChE/GSK-3β-IN-1 can be used for Alzheimer’s disease (AD) research.

COX-2-IN-67 is an orally active, blood-brain barrier permeable multi-target inhibitor that potently targets COX-2 (IC₅₀=0.07 μM), hCA IX (K_i=62.7 nM) and hBuChE (IC₅₀=0.47 μM). COX-2-IN-67 alleviates oxidative stress and liver stress, improves glucose homeostasis and insulin sensitivity, and optimizes lipid profiles. Meanwhile, COX-2-IN-67 effectively reduces the levels of neuroinflammatory markers and improves hippocampus-dependent cognitive function in a high-fat diet-induced rat model. COX-2-IN-67 can be used for the research of metabolic dysfunction-associated mild cognitive impairment.

AChE-IN-120 is a blood-brain barrier-permeable AChE inhibitor, with an IC₅₀ of 0.91 μM and a K_i of 1.027 μM against human AChE. AChE-IN-120 exerts neuroprotective effects against oxidative damage. AChE-IN-120 can be used for the research of Alzheimer's disease.

BChE-IN-6 (compound 12) is a potent BChE inhibitor, with a K_i of 0.182 μM. BChE-IN-6 shows chelating capacity on Zn²⁺. BChE-IN-6 can be used for Alzheimer’s disease (AD) research.

BuChE-IN-22 is a pseudo-irreversible butyrylcholinesterase (BuChE) inhibitor, with IC₅₀ values of 4 nM and 157 nM against hBuChE and hAChE, respectively. It also acts as a prodrug of 7-hydroxysertraline. BuChE-IN-22 releases 7-hydroxysertraline during BuChE inhibition. BuChE-IN-22 completely reverses Aβ_25-35-induced short-term and long-term memory impairments in a mouse model of Alzheimer's disease. BuChE-IN-22 can be used in research related to Alzheimer's disease.

AChE-IN-60 (compound 6k) is a potant acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitor with IC₅₀s of 27 nM and 43 nM, respectively. AChE-IN-60 also inhibits monoamine oxidase (MAO)-A and MAO-B with IC₅₀s of 353 nM and 716 nM, respectively.

BChE/p38-α MAPK-IN-2 is a BChE and p38-α MAPK dual inhibitor. BChE/p38-α MAPK-IN-2 inhibits hBChE with an IC₅₀ of 5.1 nM, showing 1000-fold selectivity over hAChE. BChE/p38-α MAPK-IN-2 inhibits p38α MAPK with an IC₅₀ of 8.12 μM. BChE/p38-α MAPK-IN-2 exhibits neuroprotective effect and can be used for the research of neurological disease, such as Alzheimer’s disease.

BChE-IN-55 is a reversible competitive inhibitor of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE), with IC₅₀ values of 2.91 μM (eqBChE) and 34.42 μM (eeAChE), respectively. BChE-IN-55 exhibits antioxidant activity. BChE-IN-55 can be used for research on Alzheimer's disease.

BChE-IN-3 (compound 45a) is a potent, selective, time-dependent and pseudoirreversible BChE inhibitor, with an IC₅₀ of 56.9 nM. BChE-IN-3 also shows marginal and reversible (not time-dependent) inhibition of AChE.

AChE/BChE-IN-30 (Compound 3g) is a Cholinesterase dual-target competitive inhibitor. AChE/BChE-IN-30 can inhibit AChE and BChE with IC₅₀ values of 0.338 and 2.087 μM and K_i values of 0.045 and 0.789 μM. AChE/BChE-IN-30 can be used for the research of neurological disease, such as Alzheimer's disease.

ChEs/MAOs-IN-2 (compound a11) is a cholinesterases and monoamine oxidases inhibitor with IC₅₀ values of 0.10, 0.20, 0.30, 0.40 µM for MAO-A, MAO-B, AChE, and BChE, respectively. ChEs/MAOs-IN-2 has the potential for the research of Alzheimer's disease.

BChE-IN-51 is a selective, blood-brain barrier-permeable, orally active BChE inhibitor with an IC₅₀ of 0.03 μM against hBChE. BChE-IN-51 reduces ROS production, protects neurons from the toxic effects of hydrogen peroxide and Aβ_1-42, and alleviates cognitive impairment. BChE-IN-51 can be used for the research of Alzheimer's disease.

Isogarcinol (Cambogin) is a potent AChE and BChE inhibitor, with IC₅₀ values of 1.13 and 8.30 μM, respectively. Isogarcinol also shows leishmanicidal activity, with an IC₅₀ of 0.33 μM against L. donovani.

hBChE-IN-4 (compound 40) is a potent hCA activator and BChE inhibitor with K_A values of 266, 76.9, 918, 893, 98.0 nM for hCA I, hCA II, hCA IV, hCA VB, hCA VII, IC₅₀ values of 72.1, 4.2 nM for eeAChE, eqBChE, respectively. hBChE-IN-4 shows no cytotoxicity. hBChE-IN-4 shows potent procognitive effects. hBChE-IN-4 has the potential for the research of neurodegenerative diseases and other neuropsychiatric disorders.

BChE-IN-42 (Compound 4a) is a BChE inhibitor with an IC₅₀ of 10.01 nM. BChE-IN-42 can be used for neurological diseases like Alzheimer's disease (AD) research.

Neuroprotective agent 15 (Compound 3e) is a neuroprotective agent. Neuroprotective agent 15 is a selective butyrylcholinesterase (BChE) inhibitor, with IC₅₀ values of 2.6 and 114.3 μM for BChE and AChE respectively. Neuroprotective agent 15 has cannabinoid CB2 receptor (CB2 receptor) agonistic activity. Neuroprotective agent 15 can reduce cell death, LDH release and Caspase-3/7 activity, and inhibit apoptosis. Neuroprotective agent 15 can reduce the formation of superoxide free radicals, maintain cell morphology, and significantly lower oxidative stress levels. Neuroprotective agent 15 can be used in the research of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

MAO-B-IN-56 is a multi-target-directed ligand with AChE, BChE, MAO-B, and BACE1 inhibitory activity, with IC₅₀ values of 0.35 μM, 3.22 μM, 0.14 μM, and 3.85 μM respectively, and shows selectivity for AChE over BChE and MAO-B over MAO-A.MAO-B-IN-56 reduces amyloid-beta production, reduces paw edema, improves spatial memory, and enhances Alzheimer's disease hallmarks and associated histopathological alterations.MAO-B-IN-56 can be used for the research of alzheimer's disease.

AChE/BuChE-IN-5 (compound 5a) is a dual target inhibitor. AChE/BuChE-IN-5 has excellent nanomolar inhibitory activity on acetylcholinesterase (AChE) (IC₅₀=46.9 nM) and butyryl cholinesterase (BuChE) (IC₅₀=3.5 nM). AChE/BuChE-IN-5 can be used for Alzheimer's Disease research.

Multitarget AD-IN-4 (compound IIIj) is a multitarget-directed ligand (MTDL), with the ability to simultaneously inhibit ChE enzymes (EeAChE IC₅₀ = 0.157 μM, eqBuChE IC₅₀ = 0.147 μM, hAChE IC₅₀ = 1.551 μM, hBuChE IC₅₀ = 2.152 μM), exhibit antioxidant activity, provide neuroprotection, and inhibit calcium channels (Ca²⁺ channel blockade: IC₅₀ = 30.59 μM). Multitarget AD-IN-4 reverses Scopolamine (HY-N0296)-induced amnesia in a mouse model. Multitarget AD-IN-4 can be used for Alzheimer’s disease (AD) research.