hAChE/hBACE-1-IN-1 (compounds 5d) is an orally active inhibitor of hAChE that can cross the blood-brain barrier. It effectively inhibits hAChE and hBACE-1, with IC50 values of 0.076 and 0.23 μM, respectively. Additionally, hAChE/hBACE-1-IN-1 prevents Aβ1-42 aggregation and enhances learning and memory in mice. This compound is useful in Alzheimer's disease research.

AChE (human):0.076 μM, BACE1 (human):0.23 μM, BCHE (human):1.204 μM

hAChE/hBACE-1-IN-1, at concentrations ranging from 10 to 80 μM over 48 hours, remains safe at its highest concentration in SH-SY5Y cells.

hAChE/hBACE-1-IN-1 administered orally at doses of 2.5-10 mg/kg over 14 days enhances learning and memory in scopolamine-induced cognitive deficit mouse models, reducing RTL and open arm time. At a dose of 500 mg/kg for 14 days, it is well tolerated with no toxicity observed in mice, including brain, liver, kidney, and heart tissues. When given at 10 mg/kg for 14 days orally, it crosses the blood-brain barrier in scopolamine-induced mice, lowering hippocampal and cortical AChE levels, and exhibits potential to delay oxidative stress and decrease pro-inflammatory cytokines. Additionally, in Aβ-induced models, it inhibits BACE-1, Aβ, APP/Aβ, and tau proteins, thereby protecting brain tissues in various regions.