Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1352, 2026 (SCI-Expanded, Scopus)
A novel series of hydroxyl‑functionalized Schiff bases was synthesized via condensation reactions of 4-morpholinoaniline with various hydroxybenzaldehydes. The resulting Schiff base ligands were subsequently transformed into novel phthalonitrile derivatives through nucleophilic aromatic substitution, employing potassium carbonate in DMF. The structures of all synthesized compounds were elucidated by FT-IR, ¹H[sbnd]NMR, and MALDI-TOF MS analyses. Cholinesterase inhibitory activities were assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Within the Schiff base series, compound MA3-SB showed the most potent AChE inhibition, with an IC₅₀ value of 11.88 nM. In contrast, the phthalonitrile derivative MA3-OFN displayed the strongest BChE inhibitory activity (IC₅₀ = 4.916 nM), suggesting preferential selectivity for the BChE active site. Molecular docking studies supported the in vitro results, revealing strong binding affinities and multiple stabilizing interactions of MA3-SB and MA3-OFN within the enzyme active sites. These findings indicate that Schiff base derivatives preferentially inhibit AChE, whereas phthalonitrile derivatives display enhanced selectivity towards BChE. The observed structure–activity relationships highlight the potential of these compounds as dual or selective cholinesterase inhibitors and provide promising scaffolds for future drug development targeting distinct stages of Alzheimer's disease.