Design, Synthesis and Biological Evaluation of Chromeno[3,4-<i>b</i>]xanthones as Multifunctional Agents for Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) remains a complex and unmet medical challenge, requiring innovative approaches to address its multifaceted pathology. In this study, we explored chromeno[3,4-b]xanthones as a novel multifunctional scaffold, synthesized via the straightforward cyclization of their precursor, (E)-2-styrylchromones. Compounds 10 and 11q-s exhibited potent and selective cholinesterase inhibition (IC₅₀ 1.7-9.0 μM for AChE and BChE), along with significant antiamyloid activity (inhibition exceeding 50% at 50 μM). Among them, compound 11r demonstrated the most well-balanced multifunctional profile against all four AD-relevant targets. Molecular docking studies revealed key π-stacking, hydrogen bonding, and halogen interactions, which un

SUBMITTER: Malafaia D 

PROVIDER: S-EPMC12818745 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature