Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection

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Joseph Arabasz MD

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May 18, 2021, 12:06:38 PM5/18/21
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Qi et al

Abstract

Butyrylcholinesterase (BChE) has been considered as a potential therapeutic function for Alzheimer’s disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close relationship with Aβ deposit. Here, we identified S06-1011 (hBChE IC50 = 16 nM) and S06-1031 (hBChE IC50 = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in Aβ1–42 peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only has a protective role against dementia but also exerts an effect on treatment and nursing care
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