BChE-IN-7

BChE-IN-7 (化合物 13) 是一种有效的、选择性的、可逆的AChE 和BChE 抑制剂。BChE-IN-7 对BChE 的IC50值为 0.06 μM。BChE-IN-7 能够穿过血脑屏障，并且保护神经元样细胞免受毒性 Aβ 物种的侵害。

AChE/BChE-IN-22 (compound 7) 作为竞争性抑制剂，对AChE和BChE酶的抑制常数分别为28.18 μM和41.74 μM。

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)

α-Amylase/α-Glucosidase-IN-7 (化合物 3f) 作为一种有效的α-amylase和α-glucosidase酶的竞争性抑制剂，其IC50值分别是18.52 µM和20.25 µM。此外，该化合物对AChE和BChE也表现出良好的抑制效果，其IC50值分别为9.25 µM和10.06 µM。α-Amylase/α-Glucosidase-IN-7 主要用于糖尿病和阿尔茨海默症相关的生物医学研究。