BuChE-IN-2

BuChE-IN-2 is an excellent butyrylcholinesterase (BuChE) inhibitor (IC50s of 1.28 μM and 0.67 μM for BuChE and NO). BuChE-IN-2 can inhibit the aggregation of Aβ, ROS formation and chelate Cu2+, exhibiting proper blood-brain barrier (BBB) penetration. BuChE-IN-2 has potential to research Alzheimer’s disease[1].

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

IC50: 1.28 μM (BuChE), 0.67 μM (NO)[1]

BuChE-IN-2 (compound f9) (5-50 μM; 24 hours) shows obvious neuroprotection on H2O2-induced PC12 cells at 20 μM[1]. BuChE-IN-2 (100 μM; 48 hours) can inhibit Aβ aggregation[1]. BuChE-IN-2 (0.1-20 μM; 24 hours) has the obviously inhibitory effect on the secretion of inflammatory factors and IL-1β (IC50=1.61 μM) and TNF-α (IC50=4.15 μM) in BV2 cells[1]. BuChE-IN-2 (1-10 μM; 1 hour) can significantly reduce the expression of COX-2 and iNOS in a concentration-dependent manner[1]. BuChE-IN-2 (1-50 μM; 6 hours) has a significant inhibitory effect on ROS accumulation at 20 μM[1]. BuChE-IN-2 (10-1000 μM; 2 hours) decreases the DPPH concentration dramatically from 86.09% to 34.62% when the concentration of BuChE-IN-2 increases from 10 μM to 1000 μM[1]. BuChE-IN-2 (75 μM; 2 hours; MDCKII-MDR1 cells) exhibits proper blood-brain barrier permeability[1]. Cell Cytotoxicity Assay Cell Line: PC12 cells[1] Concentration: 5, 20, 25, 50 μM Incubation Time: 24 hour Result: Showed obvious neuroprotection on H2O2-induced PC12 cells at 20 μM. Western Blot Analysis Cell Line: BV2 cells[1] Concentration: 1, 3, and 10 μM Incubation Time: 1 hour Result: Significantly reduced the expression of COX-2 and iNOS in a concentration-dependent manner.

BuChE-IN-2 (40.96-100 mg/kg; i.g., single) shows LD50 of 75.372 mg/kg in mice[1]. BuChE-IN-2 (10 and 30 mg/kg; i.g., single) can remarkably improve the cognitive impairment in scopolamine-induced mouse models according to Morris water maze experiment[1]. Animal Model: Male C57BL mice (8-week-old, 18-23 g)[1] Dosage: 100, 80, 64, 51.2, 40.96 mg/kg Administration: i.g.; single Result: The median Lethal Dose (LD50) of BuChE-IN-2 was 75.372 (62.383-101.673) mg/kg (95% confidence limit). Animal Model: Male C57BL mice (8-week-old, 18-23 g)[1] Dosage: 30 mg/kg, 10 mg/kg Administration: i.g., single Result: BuChE-IN-2 could remarkably improve the cognitive impairment in scopolamine-induced mouse models according to Morris water maze experiment.

[1]. Liu T, et al. Design, synthesis, and biological evaluation of novel (4-(1,2,4-oxadiazol-5-yl)phenyl)-2-aminoacetamide derivatives as multifunctional agents for the treatment of Alzheimer's disease. Eur J Med Chem. 2022;227:113973.