Rational Design, Synthesis and Pharmacological Evaluation of Chalcones as Dual-Acting Compounds-Histamine H₃ Receptor Ligands and MAO-B Inhibitors.

ABSTRACT: Chalcone-based derivatives were designed as dual-acting ligands targeting the histamine H₃ receptor (H₃R) and monoamine oxidase B (MAO-B), based on the lead compound DL76. Three series of compounds (1-18) were synthesised and characterised, including simple chalcones (1-9) and piperidinyl chalcones (10-18). All piperidinyl derivatives exhibited nanomolar affinity for human H₃R (hH₃R), with compounds 10-12 achieving K_i values ≤ 30 nM. Simple chalcones showed potent human MAO-B (hMAO-B) inhibition (IC₅₀: 0.85-337 nM), especially 3,4-dichloro derivatives. Compound 15 was the most active hybrid, with a K_i of 46.8 nM for hH₃R and an IC

SUBMITTER: Lazewska D 

PROVIDER: S-EPMC12840679 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature