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Alzheimer’s disease (AD) is a multifactorial neurodegenerative condition of the central nervous system (CNS) that is currently treated by cholinesterase inhibitors and the <i>N</i>-methyl-<span style="font-variant: small-caps;">d</span>-aspartate receptor antagonist, memantine. Emerging evidence strongly supports the relevance of targeting butyrylcholinesterase (BuChE) in the more advanced stages of AD. Within this study, we have generated a pilot series of compounds (<b>1</b>–<b>20</b>) structurally inspired from belladine-type Amaryllidaceae alkaloids, namely carltonine A and B, and evaluated their acetylcholinesterase (AChE) and BuChE inhibition properties. Some of the compounds exhibited intriguing inhibition activity for human BuChE (<i>h</i>BuChE), with a preference for BuChE over AChE. Seven compounds were found to possess a <i>h</i>BuChE inhibition profile, with IC₅₀ values below 1 µM. The most potent one, compound <b>6</b>, showed nanomolar range activity with an IC₅₀ value of 72 nM and an excellent selectivity pattern over AChE, reaching a selectivity index of almost 1400. Compound <b>6</b> was further studied by enzyme kinetics, along with in-silico techniques, to reveal the mode of inhibition. The prediction of CNS availability estimates that all the compounds in this survey can pass through the blood-brain barrier (BBB), as disclosed by the BBB score.