Akademik Veri Yönetim Sistemi
Tetrahedron, cilt.196, 2026 (SCI-Expanded, Scopus)
We report the design and development of a new series of cholinesterase inhibitors by synthesizing and evaluating quinoline-based hybrid heterocyclic compounds. Polyheterocyclic 4H-pyran derivatives (4a-f) were prepared using a one-pot condensation reaction. This process yielded novel quinoline derivatives, including quinoline-4H-benzo[b]pyran and quinoline-pyrano-pyrazole compounds, thoroughly characterized using diverse spectroscopic techniques and analytical methods analysis confirmed successful cyclization and the preservation of the quinoline core. Biological evaluation revealed significant anticholinesterase activity, with compound 4a demonstrating potent AChE inhibition (IC50 = 16.27 ± 0.65 μM) and 4e exhibiting exceptional BChE inhibition (IC50 = 0.67 ± 0.11 μM), surpassing the reference drug Galantamine. Selectivity index analysis indicated marked BChE selectivity for 4e and 4f, whereas 4b displayed dual inhibitory activity. Molecular docking studies provided mechanistic insight, revealing key interactions with catalytic residues in AChE (Ser203, Glu202, Tyr72) and BChE (Ser198, His438, Thr120), supporting the experimental selectivity profiles. The study highlights the therapeutic potential of these quinoline–4H-pyran hybrids as a versatile and potent scaffold for selective and dual cholinesterase inhibition, and emphasizes the influence of structural modifications on activity offering a promising foundation for the development of novel therapeutic agents targeting Alzheimer's disease. Further optimization and in vivo studies are needed to improve potency, selectivity, and central nervous system activity, paving the way for Alzheimer's treatments.