Multifunctional Tacrine-Quinoline Hybrids as Cholinesterase Inhibitors, Aβ Aggregation Blockers, and Metal Chelators for Alzheimer's Therapy.

ABSTRACT: A novel series of multifunctional tacrine-quinoline hybrids were designed, synthesized, and evaluated as potential anti-Alzheimer's agents. These compounds incorporate tacrine for cholinesterase's inhibition and 8-hydroxyquinoline for metal chelation. Piperazine was selected as a linker to provide conformational flexibility and to create favorable cation-π interactions with residues in the mid-gorge region of AChE, enhancing dual-site binding with AChE to inhibit Aβ aggregation. In vitro studies demonstrated submicromolar inhibitory activity toward both AChE and BuChE, particularly for compounds 16e (IC₅₀ = 0.10 μM for AChE, 0.043 μM for BuChE) and 16h (IC₅₀ = 0.21 μM for AChE, 0.10 μM for BuChE). These compounds also exhibited potent inhibition of self-

SUBMITTER: Wang X 

PROVIDER: S-EPMC12430544 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature