The Chemotype of Chromanones as a Privileged Scaffold for Multineurotarget Anti-Alzheimer Agents

The multifactorial nature of Alzheimer's disease necessitates the development of agents able to interfere with different relevant targets. A series of 22 tailored chromanones was conceptualized, synthesized, and subjected to biological evaluation. We identified one representative bearing a linker-connected azepane moiety (compound 19) with balanced pharmacological properties. Compound 19 exhibited inhibitory activities against human acetyl-, butyrylcholinesterase and monoamine oxidase-B, as well as high affinity to both the sigma 1 and sigma 2 receptors. Our study provides a framework for the development of further chromanone-based multineurotarget agents.

Automated summary

The multifactorial nature of Alzheimer's disease necessitates the development of agents that can target multiple relevant pathways. In this study, we synthesized a series of tailored chromanones and evaluated their biological activities. One representative compound (compound 19) was identified, which exhibited balanced pharmacological properties and showed inhibitory activities against acetylcholinesterase, butyrylcholinesterase, monoamine oxidase-B, and high affinity to sigma 1 and sigma 2 receptors. Our findings provide a framework for the development of chromanone-based multineurotarget agents.