AChE/MAO-B-IN-9

AChE/MAO-B-IN-9 (Compound E12) is an orally active, selective, reversible, non-competitive inhibitor of AChE and MAO-B, with an IC50 of 0.156 μM for electric eel AChE. It inhibits Aβ40/42 fibril formation, promotes the depolymerization of Aβ fibrils, and suppresses Tau protein fibril formation. Additionally, AChE/MAO-B-IN-9 exhibits antioxidant and neuroprotective properties and improves memory impairment induced by Scopolamine in mice. This compound is applicable in Alzheimer's disease research.

EeAChE:0.156 μM

AChE/MAO-B-IN-9 (12 min) serves as a potent inhibitor of electric eel AChE with an IC50 of 0.156 ± 0.11 μM, exhibiting 36.79 times greater selectivity for AChE over BuChE. At a concentration of 1 μM for 60 minutes, AChE/MAO-B-IN-9 reduces the activity of mouse liver mitochondrial MAO-B by 54.9 ± 2.7%. In the range of 0.625-10 μM for up to 80 hours, it inhibits Aβ40 fibril formation in a concentration-dependent manner, with an IC50 of 10.00 μM, and similarly, it strongly suppresses Aβ42 fibril formation with an IC50 of 1.01 μM. For Tau protein fibril formation, AChE/MAO-B-IN-9 (2.5-10 μM for up to 50 hours) shows an IC50 of 4.50 μM and reduces the plateau phase fluorescence intensity by 49% at 10 μM. Additionally, the compound inhibits Aβ secretion from SH-SY5Y cells in a concentration-dependent manner, achieving approximately 80% inhibition of total Aβ after 24 hours at 20 μM.

Administered orally at doses ranging from 1 to 5 mg/kg once daily for seven days, AChE/MAO-B-IN-9 can dose-dependently enhance spatial memory deficits induced by Scopolamine in male ICR mice.